Integrated disease diagnosis and treatment system

ABSTRACT

Designs, implementations, and techniques for optically measuring a sample and integrated systems that provide CT-scan, optical probing and therapy by electromagnetic radiation treatment (e.g. laser, RF, or microwave). Light at different wavelength bands may be used to detect different absorption features in the sample. Multiple light sources may be used including tunable lasers.

This application claims the benefit of the U.S. Provisional PatentApplication Ser. No. 60/620,793 entitled “Early-Stage Lung CancerDiagnosis and Treatment System” and filed on Oct. 20, 2004.

This application is a continuation-in-part application of and claims thebenefit of U.S. application Ser. No. 10/963,948 entitled“Coherence-Gated Optical Glucose Monitor” and filed on Oct. 12, 2004 nowU.S. Pat. No. 7,263,394 which was published as U.S. patent publicationNo. US-2005-0075547-A1 on Apr. 7, 2005.

This application is also a continuation-in-part application of andclaims the benefit of pending U.S. application Ser. No. 11/244,418entitled “Cross-Sectional Mapping of Spectral Absorbance Features” andfiled on Oct. 4, 2005.

The entire disclosures of the above-referenced patent applications areincorporated herein by reference as part of the specification of thisapplication.

BACKGROUND

This application relates to devices and techniques for non-invasiveoptical probing of various substances, and devices, systems and methodsfor detecting, diagnosing and treating lung disease using thenon-invasive optical probing.

Investigation of substances by non-invasive and optical means has beenthe object of many studies as inhomogeneity of light-matter interactionsin substances can reveal their structural, compositional, physiologicaland biological information. Various devices and techniques based onoptical coherence domain reflectometry (OCDR) may be used fornon-invasive optical probing of various substances, including but notlimited to skins, body tissues and organs of humans and animals, toprovide tomographic measurements of these substances.

In many OCDR systems, the light from a light source is split into asampling beam and a reference beam which propagate in two separateoptical paths, respectively. The light source may be partially coherentsource. The sampling beam is directed along its own optical path toimpinge on the substances under study, or sample, while the referencebeam is directed in a separate path towards a reference surface. Thebeams reflected from the sample and from the reference surface are thenbrought to overlap with each other to optically interfere. Because ofthe wavelength-dependent phase delay the interference results in noobservable interference fringes unless the two optical path lengths ofthe sampling and reference beams are very similar. This provides aphysical mechanism for ranging. A beam splitter may be used to split thelight from the light source and to combine the reflected sampling beamand the reflected reference beam for detection at an optical detector.This use of the same device for both splitting and recombining theradiation is essentially based on the well-known Michelsoninterferometer. The discoveries and the theories of the interference ofpartially coherent light are summarized by Born and Wolf in “Principlesof Optics”, Pergamon Press (1980).

Low-coherence light in free-space Michelson interferometers was utilizedfor measurement purposes. Optical interferometers based on fiber-opticcomponents were used in various instruments that use low-coherence lightas means of characterizing substances. Various embodiments of thefiber-optic OCDR exist such as devices disclosed by Sorin et al in U.S.Pat. No. 5,202,745, by Marcus et al in U.S. Pat. No. 5,659,392, byMandella et al in U.S. Pat. No. 6,252,666, and by Tearney et al in U.S.Pat. No. 6,421,164. The application of OCDR in medical diagnoses incertain optical configurations has come to be known as “opticalcoherence tomography” (OCT).

FIG. 1 illustrates a typical optical layout used in many fiber-opticOCDR systems described in U.S. Pat. No. 6,421,164 and otherpublications. A fiber splitter is attached to two optical fibers thatrespectively guide the sampling and reference beams in a Michelsonconfiguration. Common to many of these and other implementations, theoptical radiation from the low-coherence source is first physicallyseparated into two separate beams where the sampling beam travels in asample waveguide to interact with the sample while the reference beamtravels in a reference waveguide. The fiber splitter than combines thereflected radiation from the sample and the reference light from thereference waveguide to cause interference.

SUMMARY

This application describes devices, systems and techniques that usenon-invasive optical probing and integrated medical diagnosis andtreatment systems and techniques based on the non-invasive opticalprobing. In one implementation, for example, an integrated diagnosticand treatment system is described to include a CT scan unit to locateailing areas in a body part, a referenced cross-sectional imaging unitto analyze each ailing area, and a laser, RF or microwave irradiationtherapy unit to treat a selected ailing area. In another implementation,this application describes an integrated diagnostic/therapeutic systemfor lung cancer treatment which includes a CT scan unit to locatepulmonary nodule locations; a referenced cross-sectional imaging unit toanalyze each pulmonary nodule location; and a laser irradiation therapyunit to optically treat a selected pulmonary nodule location. In yetanother implementation, an integrated diagnostic and treatment system isdescribed to include a CT scan unit to locate pulmonary nodulelocations; a referenced cross-sectional imaging unit to analyze eachpulmonary nodule location; and a microwave ablation therapy unit totreat a selected pulmonary nodule location.

Specific implementations of the above systems and devices are alsodescribed. In one example, a medical device includes a bronchoscopecomprising a working channel configured for insertion into a passage ofa body to reach a target area inside the body; an optical fiber probemodule comprising (1) a probe optic fiber having a portion inserted intothe working channel of the bronchoscope and (2) an optical probe headcoupled to an end of the probe optic fiber and located inside theworking channel, the optical fiber probe device operable to direct probelight to and collect reflected light from the target area in the bodythrough the probe optic fiber and the optical probe head and to furtherobtain information of the target area from the collected reflectedlight; and a laser therapy module comprising a power delivery opticfiber having a portion inserted into the working channel of thebronchoscope to deliver a treatment laser beam to the target area.

A method for diagnosing and treating a malignant condition of a patientis also described to include performing a computed tomography (CT) scanin a selected body part of the patient to identify locations in theselected body part that are potentially malignant; using an opticalprobe beam to optically probe the identified locations to furtheridentify malignant locations from benign locations; and deliveringradiation energy to each identified malignant location to treat amalignant condition.

This application also describes methods and apparatus for theacquisition of optical spectral absorbance features and theirdistribution in the cross sections of tissues and other samples usingmultiple light sources emitting light centered at different wavelengths.In one example, a method for optically measuring a sample is described,where different light sources emitting light at different wavelengthsare used to measure the sample. The light at each and every wavelengthfrom the different light sources is directed through a single, commonwaveguide in a first propagation mode to one sampling location of asample. The first portion of the guided light in the first propagationmode at a location near the sample is directed away from the samplebefore the first portion reaches the sample while allowing a secondportion in the first propagation mode to reach the sample. A reflectionof the second portion from the sample is directed to be in a secondpropagation mode different from the first propagation mode to produce areflected second portion. Both the reflected first portion in the firstpropagation mode and the reflected second portion in the secondpropagation mode are then directed through the single waveguide. Arelative delay between the reflected first portion and the reflectedsecond portion received from the single waveguide is produced. Therelative delay between the reflected first portion and the reflectedsecond portion received from the single waveguide are adjusted at twodifferent bias values to select a layer of material inside the sample tomeasure an optical absorption of the selected layer at each and everywavelength from the different light sources. The light at each and everywavelength from the different light sources is directed through thesingle waveguide to other sampling locations of the sample to measurethe optical absorption of the selected layer at each and everywavelength from the different light sources at each of the samplinglocations.

In another example, a device is described to include radiation sourcesto produce radiation beams at different wavelengths, respectively. Amultiplexer is used to receive the radiation beams from the radiationsources and to combine the radiation beams to propagate along a commonpath. A delivery module is used to direct a part of the combinedradiation to a sample and to collect reflected radiation from the samplewhile reflecting the radiation that does not reach the sample in itsvicinity. This device also includes a controllable differential delaydevice to receive both the reflected radiation from the sample andreflected radiation that does not reach the sample. A demultiplexer isincluded in this device to receive radiation from the differential delaydevice and to separate received radiation into a plurality of beams atdifferent wavelengths. The device further includes radiation detectorspositioned to respectively receive the beams from the demultiplexer.

In another example, a device described in this application includesmeans for combining and guiding optical radiation from a plurality oflight sources, each emitting at wavelengths within a spectral banddifferent from others, towards a sample through a common opticalwaveguide; means for reflecting a first portion of the combinedradiation away from the sample at its vicinity while directing a secondportion of the combined radiation to reach the sample; means forcollecting and guiding at least part of the reflected first portion andat least part of a reflected second portion from the sample towards adetection module through the common optical waveguide; means forseparating the light into a plurality of spectral bands corresponding toemitting spectral bands of the light sources; and means for directinglight radiation of the separated spectral bands to a plurality of lightdetectors, respectively.

This application also describes an example of a device for opticallymeasuring a sample to include light sources emitting light at differentwavelength bands centered at different wavelengths, a single waveguideto receive and guide the light at the different wavelength bands in afirst propagation mode, and a probe head coupled to the waveguide toreceive the light from the waveguide and to reflect a first portion ofthe light back to the waveguide in the first propagation mode and directa second portion of the light to a sample. The probe head collectsreflection of the second portion from the sample and exports to thewaveguide the reflection as a reflected second portion in a secondpropagation mode different from the first propagation mode. This devicealso includes an optical differential delay unit to produce and controla relative delay between the first propagation mode and the secondpropagation mode in response to a control signal, and a detection moduleto receive the reflected light radiation in the first and secondpropagation modes to extract information of the sample carried by thereflected light in the second propagation mode and a control unit. Thecontrol unit produces the control signal to the optical differentialdelay unit and sets the relative delay at two different bias values toselect a layer of material inside the sample to measure an opticalabsorption of the selected layer at each and every wavelength from thedifferent light sources. In one implementation, the detection module maybe configured to include an optical device to convert a part of receivedlight in the first propagation mode and a part of received light in thesecond propagation mode into light in a third propagation mode thatpropagates along a first optical path. This optical device also convertsremaining portions of the received light in the first and the secondpropagation modes into light in a fourth propagation mode thatpropagates along a second, different optical path. The detection modulealso includes a first optical element in the first optical path toseparate light at different wavelength bands into a first set ofdifferent beams, first light detectors to respectively receive anddetector the first set of different beams from the first opticalelement, a second optical element in the second optical path to separatelight at different wavelength bands into a second set of differentbeams, and second light detectors to respectively receive and detectorthe second set of different beams from the second optical element.

In yet another example, a device for optically measuring a sample isdescribed to include tunable laser sources emitting light at differentwavelength bands centered at different wavelengths. A single waveguideis included to receive and guide the light at the different wavelengthbands in a first propagation mode. A probe head is coupled to thewaveguide to receive the light from the waveguide and to reflect a firstportion of the light back to the waveguide in the first propagation modeand direct a second portion of the light to a sample. The probe headcollects reflection of the second portion from the sample and exports tothe waveguide the reflection as a reflected second portion in a secondpropagation mode different from the first propagation mode. A detectionmodule is included to receive the reflected light in the first and thesecond propagation modes in the waveguide and to extract information ofthe sample carried by the reflected light in the second propagationmode. A control unit is also included to tune each tunable laser througha corresponding wavelength band to obtain absorption measurements of thesample at different wavelengths within each corresponding wavelengthband.

The designs, techniques and exemplary implementations for non-invasiveoptical probing described in this application use the superposition andinteraction of different optical modes propagating along substantiallythe same optical path inside one or more common optical waveguides. Whenone of the optical modes interacts with the substance under study, itssuperposition with the other mode can be used for the purpose ofacquiring information about the optical properties of the substance.

The methods and apparatus described in this application are at least inpart based on the recognition of various technical issues and practicalconsiderations in implementing OCDR in commercially practical and userfriendly apparatus, and various technical limitations in OCDR systemsdisclosed by the above referenced patents and other publications. As anexample, at least one of disadvantages associated to the OCDR systemdesigns shown in FIG. 1 or described in the aforementioned patents isthe separation of the reference light beam from the sample light beam.Due to the separation of the optical paths, the relative optical phaseor differential delay between the two beams may experience uncontrolledfluctuations and variations, such as different physical length,vibration, temperature, waveguide bending and so on. When the sample armis in the form of a fiber-based catheter that is separate from thereference arm, for example, the manipulation of the fiber may cause asignificant fluctuation and drift of the differential phase between thesample and reference light beams. This fluctuation and draft mayadversely affect the measurements. For example, the fluctuation anddrift in the differential phase between the two beams may lead totechnical difficulties in phase sensitive measurements as absolutevaluation of refractive indices and measurements of birefringence.

In various examples described in this application, optical radiation isnot physically separated to travel different optical paths. Instead, allpropagation waves and modes are guided along essentially the sameoptical path through one or more common optical waveguides. Such designswith the common optical path may be advantageously used to stabilize therelative phase among different radiation waves and modes in the presenceof environmental fluctuations in the system such as variations intemperatures, physical movements of the system especially of thewaveguides, and vibrations and acoustic impacts to the waveguides andsystem. In this and other aspects, the present systems are designed todo away with the two-beam-path configurations in variousinterferometer-based systems in which sample light and reference lighttravel in different optical paths. Implementations of the presentsystems may be configured to significantly reduce the fluctuations anddrifts in the differential phase delay and to benefit somephase-sensitive measurements, such as the determination of the absolutereflection phase and birefringence. In addition, the techniques anddevices described in this application simplify the structures and theoptical configurations of devices for optical probing by using thecommon optical path to guide light.

In various applications, it may be beneficial to acquire the absorptioncharacteristics of the material in an isolated volume inside the sample.In other case it may be desirable to map the distribution of somesubstances identifiable through their characteristic spectralabsorbance. In some OCDR systems such as systems in aforementionedpatents, it may be difficult to perform direct measurements of theoptical inhomogeneity with regard to these and other spectralcharacteristics. The systems and techniques described in thisapplication may be configured to allow for direct measurements of theseand other spectral characteristics of a sample.

Exemplary implementations are described below to illustrate variousfeatures and advantages of the systems and techniques. One of suchfeatures is methods and apparatus for acquiring information regardingoptical inhomogeneity in substance by a non-invasive means with the helpof a low-coherence radiation. Another feature is to achieve high signalstability and high signal-to-noise ratio by eliminating the need ofsplitting the light radiation into a sample path and a reference path.Additional features include, for example, a platform on whichphase-resolved measurements such as birefringence and absoluterefractive indices can be made, capability of acquiring opticalinhomogeneity with regard to the spectral absorbance, solving theproblem of signal drifting and fading caused by the polarizationvariation in various interferometer-based optical systems, and aneffective use of the source radiation with simple optical arrangements.Advantages of the systems and techniques described here include, amongothers, enhanced performance and apparatus reliability, simplifiedoperation and maintenance, simplified optical layout, reduced apparatuscomplexity, reduced manufacturing complexity and cost.

Various exemplary methods and techniques for optically sensing samplesare described. In some implementations, input light in two differentoptical propagation modes (e.g., the first and second modes) is directedthrough a common input optical path to the optical probe head whichsends a portion of input light in the second mode to the sample. Theprobe head directs both the light in the first mode and the returnedlight from the sample in the second mode through a common optical pathto a detection module.

For example, one method described here includes the following steps.Optical radiation in both a first propagation mode and a second,different propagation mode are guided through an optical waveguidetowards a sample. The radiation in the first propagation mode isdirected away from the sample without reaching the sample. The radiationin the second propagation mode is directed to interact with the sampleto produce returned radiation from the interaction. Both the returnedradiation in the second propagation mode and the radiation in the firstpropagation mode are coupled into the optical waveguide away from thesample. Next, the returned radiation in the second propagation mode andthe radiation in the first propagation mode from the optical waveguideare used to extract information of the sample.

As another example, a device for optically measuring a sample isdescribed to include a waveguide, a probe head, and a detection module.The waveguide supports a first propagation mode and a second, differentpropagation mode and is used to receive and guide an input beam in boththe first and the second propagation modes. The probe head is coupled tothe waveguide to receive the input beam and to reflect a first portionof the input beam in the first propagation mode back to the waveguide inthe first propagation mode and direct a second portion of the input beamin the second propagation mode to a sample. The probe head collectsreflection of the second portion from the sample and exports to thewaveguide the reflection as a reflected second portion in the secondpropagation mode. The detection module is used to receive the reflectedfirst portion and the reflected second portion in the waveguide and toextract information of the sample carried by the reflected secondportion.

This application also describes devices that use one input waveguide todirect input light to the optical probe head and another outputwaveguide to direct output from the optical probe head. For example, adevice for optically measuring a sample may include an input waveguide,which supports a first propagation mode and a second, differentpropagation mode, to receive and guide an input beam in both the firstand the second propagation modes. The device may also include an outputwaveguide which supports the first and the second propagation modes. Inthis device, a probe head may be coupled to the input waveguide toreceive the input beam and to the output waveguide, the probe headoperable to direct a first portion of the input beam in the firstpropagation mode into the output waveguide in the first propagation modeand direct a second portion of the input beam in the second propagationmode to a sample. The probe head collects reflection of the secondportion from the sample and exports to the output waveguide thereflection as a reflected second portion in the second propagation mode.In addition, a detection module may be included in this device toreceive the reflected first portion and the reflected second portion inthe output waveguide and to extract information of the sample carried bythe reflected second portion.

In some other implementations, light in a single optical propagationmode, e.g., a first predetermined mode, is directed to an optical probehead near the sample under measurement. The optical probe head directs afirst portion of the input light away from the sample in the first modeand a second portion of the input light to the sample. The optical probehead then directs returned light from the sample in a second, differentmode to co-propagate along with the first portion in the first mode in acommon optical path.

For example, one method for optically measuring a sample includes thefollowing steps. A beam of guided light in a first propagation mode isdirected to a sample. A first portion of the guided light in the firstpropagation mode is directed away from the sample at a location near thesample before the first portion reaches the sample. A second portion inthe first propagation mode is directed to reach the sample. A reflectionof the second portion from the sample is controlled to be in a secondpropagation mode different from the first propagation mode to produce areflected second portion. Both the reflected first portion in the firstpropagation mode and the reflected second portion in the secondpropagation mode are then directed through a common waveguide into adetection module to extract information from the reflected secondportion on the sample.

Another method for optically measuring a sample is also described. Inthis method, light in a first propagation mode is directed to a vicinityof a sample under measurement. A first portion of the light in the firstpropagation mode is then directed to propagate away from the sample atthe vicinity of the sample without reaching the sample. A second portionof the light in the first propagation mode is directed to the sample tocause reflection at the sample. The reflected light from the sample iscontrolled to be in a second propagation mode that is independent fromthe first propagation mode to co-propagate with the first portion alonga common optical path. The first portion in the first propagation modeand the reflected light in the second propagation mode are used toobtain information of the sample.

This application further describes exemplary implementations of devicesand systems for optically measuring samples where optical probe headsreceive input light in one mode and outputs light in two modes. Oneexample of such devices includes a waveguide to receive and guide aninput beam in a first propagation mode, and a probe head coupled to thewaveguide to receive the input beam and to reflect a first portion ofthe input beam back to the waveguide in the first propagation mode anddirect a second portion of the input beam to a sample. This probe headcollects reflection of the second portion from the sample and exports tothe waveguide the reflection as a reflected second portion in a secondpropagation mode different from the first propagation mode. This devicefurther includes a detection module to receive the reflected firstportion and the reflected second portion in the waveguide and to extractinformation of the sample carried by the reflected second portion.

In another example, an apparatus for optically measuring a sample isdisclosed to include a light source, a waveguide supporting at least afirst and a second independent propagation modes and guiding the lightradiation from the light source in the first propagation mode to thevicinity of a sample under examination, a probe head that terminates thewaveguide in the vicinity of the sample and reverses the propagationdirection of a portion of the first propagation mode in the waveguidewhile transmitting the remainder of the light radiation to the sample,the probe head operable to convert reflected light from the sample intothe second propagation mode, and a differential delay modulator thattransmits the light in both the first and the second propagation modesfrom the probe head and the waveguide and varies the relative opticalpath length between the first and the second propagation modes. In thisapparatus, a mode combiner is included to receive light from thedifferential delay modulator and operable to superpose the first and thesecond propagation modes by converting a portion of each mode to a pairof new modes. At least one photodetector is used in this apparatus toreceive light in at least one of the two new modes. Furthermore, anelectronic controller is used in communication with the photodetectorand is operable to extract information of the sample from the output ofthe photodetector.

In yet another example, a device is described to include an opticalwaveguide, an optical probe head and an optical detection module. Theoptical waveguide is to guide an optical radiation in a first opticalmode. The optical probe head is coupled to the optical waveguide toreceive the optical radiation. The optical probe head is operable to (1)redirect a portion of the optical radiation back to the opticalwaveguide while transmitting the remaining radiation to a sample, (2)receive and direct the reflected or backscattered radiation from thesample into the waveguide, and (3) control the reflected or thebackscattered light from the sample to be in a second optical modedifferent from the first optical mode. The optical detection module isused to receive the radiation redirected by the probe head through thewaveguide and to convert optical radiation in the first and secondoptical modes, at least in part, into a common optical mode.

A further example of a device for optically measuring a sample includesan input waveguide, an output waveguide and a probe head. The inputwaveguide supports a first and a second different propagation modes andis used to receive and guide an input beam in the first propagationmode. The output waveguide supports a first and a second differentpropagation modes. The probe head is coupled to the input waveguide toreceive the input beam and to the output waveguide to export light. Theprobe head is operable to direct a first portion of the input beam inthe first propagation mode into the output waveguide and direct a secondportion of the input beam to a sample. In addition, the probe headcollects reflection of the second portion from the sample and exports tothe output waveguide the reflection as a reflected second portion in thesecond propagation mode. Furthermore, this device includes a detectionmodule to receive the reflected first portion and the reflected secondportion in the output waveguide and to extract information of the samplecarried by the reflected second portion.

This application also describes an example of an apparatus for opticallymeasuring a sample. In this example, a first waveguide capable ofmaintaining at least one propagation mode is used. A light source thatemits radiation is used to excite the propagation mode in the firstwaveguide. A light director is used to terminate the first waveguidewith its first port, to pass the light mode entering the first port, atleast in part, through a second port, and to pass the light modesentering the second port, at least in part, through a third port. Theapparatus also includes a second waveguide that supports at least twoindependent propagation modes and having a first end coupled to thesecond port and a second end. Notably, a probe head is coupled to thesecond end of the second waveguide and operable to reverse thepropagation direction of the light in part back to the second waveguideand to transmit the remainder to the sample. This probe head is operableto transform the collected light from the sample reflection to anorthogonal mode supported by the second waveguide and direct light inthe orthogonal mode into the second waveguide. A third waveguide is alsoincluded which supports at least two independent propagation modes andis connected to the third port of the light director to receive lighttherefrom. A differential delay modulator is used to connect to thethird waveguide to receive light from the second waveguide and imposes avariable phase delay and a variable path length on one mode in referenceto the other. A fourth waveguide supporting at least two independentmodes is coupled to the differential delay modulator to receive lighttherefrom. A detection subsystem is positioned to receive light from thefourth waveguide and to superpose the two propagation modes from thefourth waveguide to form two new modes, mutually orthogonal. Thisdetection subsystem includes two photo-detectors respectively receivinglight in the new modes.

Furthermore, this application describes optical sensing devices andsystems that direct input light in a single propagation mode to theoptical probe head and use the optical probe head to direct both lightthat does not reach the sample and light that is returned from thesample in the same mode and along a common propagation path which may beformed of one or more connected waveguides towards the detection module.For example, a device based on this aspect may include a waveguide whichsupports at least an input propagation mode of light, a probe headcoupled to the waveguide, and a detection module. The waveguide is usedto receive and guide an input beam in the input propagation mode. Theprobe head is used to receive the input beam and to reflect a firstportion of the input beam back to the waveguide in the input propagationmode and direct a second portion of the input beam in the inputpropagation mode to a sample. The probe head collects reflection of thesecond portion from the sample and exports to the waveguide thereflection as a reflected second portion in the input propagation mode.The detection module is used to receive the reflected first portion andthe reflected second portion in the input propagation mode from thewaveguide and to extract information of the sample carried by thereflected second portion.

These and other features, system configurations, associated advantages,and implementation variations are described in detail in the attacheddrawings, the textual description, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an example of a conventional optical sensing device basedon the well-known Michelson interferometer with reference and samplebeams in two separate optical paths.

FIG. 2 shows one example of a sensing device according to oneimplementation.

FIG. 3 shows an exemplary implementation of the system depicted in FIG.2.

FIG. 4 shows one exemplary implementation of the probe head and oneexemplary implementation of the polarization-selective reflector (PSR)used in FIG. 3.

FIGS. 5A and 5B illustrate another exemplary optical sensing system thatuse three waveguides and a light director to direct light in two modesto and from the probe head in measuring a sample.

FIG. 6 illustrates the waveform of the intensity received at thedetector in the system in FIGS. 5A and 5B as a function of the phasewhere the detected light intensity exhibits an oscillating waveform thatpossesses a base frequency and its harmonics.

FIG. 7 shows one exemplary operation of the described system in FIG. 5Bor the system in FIG. 3 for acquiring images of optical inhomogeneity.

FIGS. 8A and 8B illustrate one exemplary design of the optical layout ofthe optical sensing system and its system implementation with anelectronic controller where light in a single mode is used as the inputlight.

FIG. 9 shows another example of a system implementation where theoptical probe head receives light in a single input mode and convertspart of light into a different mode.

FIGS. 10A and 10B show two examples of the possible designs for theprobe head used in sensing systems where the input light is in a singlemode.

FIG. 11 shows one implementation of a light director that includes apolarization-maintaining optical circulator and two polarization beamsplitters.

FIG. 12 illustrates an example of the optical differential delaymodulator used in present optical sensing systems where an externalcontrol signal is applied to control a differential delay element tochange and modulate the relative delay in the output.

FIGS. 12A and 12B illustrate two exemplary devices for implementing theoptical differential delay modulator in FIG. 12.

FIGS. 13A and 13B illustrate two examples of a mechanical variable delayelement suitable for implementing the optical differential delaymodulator shown in FIG. 12B.

FIG. 14A shows an exemplary implementation of the delay device in FIG.12B as part of or the entire differential delay modulator.

FIG. 14B shows a delay device based on the design in FIG. 14A where themirror and the variable optical delay line are implemented by themechanical delay device in FIG. 13A.

FIG. 15 illustrates an optical sensing system as an alternative to thedevice shown in FIG. 5B.

FIG. 16 shows a system based on the design in FIG. 2 where a tunablefilter is inserted in the input waveguide to filter the input light intwo different modes.

FIG. 17 shows another exemplary system based on the design in FIG. 8Awhere a tunable filter is inserted in the input waveguide to filter theinput light in a single mode.

FIG. 18 illustrates the operation of the tunable bandpass filter in thedevices in FIGS. 16 and 17.

FIG. 19A illustrates an example of a human skin tissue where the opticalsensing technique described here can be used to measure the glucoseconcentration in the dermis layer between the epidermis and thesubcutaneous layers.

FIG. 19B shows some predominant glucose absorption peaks in blood in awavelength range between 1 and 2.5 microns.

FIG. 20 illustrates one exemplary implementation of the detectionsubsystem in FIG. 3 where two diffraction gratings are used to separatedifferent spectral components in the output light beams from thepolarizing beam splitter.

FIGS. 21 and 22 shows examples of optical sensing devices that directlight in a single mode to the optical probe head and direct output lightfrom the probe head in the same single mode.

FIG. 23 shows an example of a design for the optical probe head for thedevices in FIGS. 21 and 22 where the optical probe head does not changethe mode of light.

FIG. 24 illustrates two selected surfaces underneath a surface of a bodypart in optical spectral absorbance mapping measurements.

FIGS. 25, 26 and 27 show examples of devices that use multiple lightsources at fixed center emitting wavelengths for spectral absorbancemapping measurements.

FIG. 28 shows one example of an optical multiplexer to combine beamsfrom different light sources into a common waveguide or optical path.

FIGS. 29A and 29B show another example of an optical multiplexer withdichroic filters to combine beams from different light sources into acommon waveguide or optical path and the spectral properties of thedichroic filters.

FIG. 30 shows an exemplary device that uses multiple light sources atfixed center emitting wavelengths for spectral absorbance mappingmeasurements, where an optical switch is used to sequentially directdifferent beams from different light sources into a common waveguide oroptical path.

FIG. 31 illustrates an example for using different beams at differentwavelengths to detect an absorption feature in a sample in spectralabsorbance mapping measurements.

FIG. 32 shows an exemplary device that uses multiple tunable lightsources for spectral absorbance mapping measurements.

FIG. 33 shows an example of an integrated system that combines an X-rayCT scan module, a reference cross-sectional tissue imaging module, and alaser treatment module to provide a complete diagnostic and treatmentplatform for treating lung cancer.

FIG. 34 shows one exemplary use of the system in FIG. 33 in detectingand treating lung cancer.

FIG. 35 shows a tubular unit or sheath for holding the probe fiber andthe waveguide together as a single unit inserted inside the workingchannel shown in FIG. 33.

DETAILED DESCRIPTION

Lung cancer is one of the most deadly cancers in the United States.Patients with lung cancer have a relatively low 5-year survival rate ofonly 10-15% after diagnosis. The lung cancer in many patients is alreadyin the second or third stage and has metastasized to other sites ororgans by the time they begin to exhibit symptoms and seek medicaltreatment. Few are diagnosed in early stages where the survival rate canbe much higher, approaching 85% for the stage 1 lung cancer. Theconventional annual chest X-ray examination has not shown sufficientsensitivity to reveal the isolated, small (e.g., less than 1 centimeterin diameter) tumors typically found in the stage 1 lung cancer.

Recently, emphasis has shifted to early stage detection in majorEuropean and Japanese studies. In the US, a major new trial, theNational Lung Screening Trial (NLST), has begun and is aimed atevaluating the efficacy of thoracic Computed Tomography (CT) scans indetecting early stage lung cancer. The NLST will compare a randomlyselected group of high risk subjects (ex-smokers) who receive annual CTscans to a control group of subjects receiving chest x-rays.

The results of early studies have shown that thoracic CT scans oftenrevealed a substantial number of solitary pulmonary nodules (SPNs).Biopsies have shown that approximately 80% or greater (e.g., 98%) ofthese SPNs were calcified and benign. However, the CT scan could notdistinguish between calcified SPNs and active SPNs. The inability of theCT scans to distinguish malignancies from benign SPNs has led to avigorous debate as to the efficacy of the CT scans in early screeningfor lung cancer.

A remedy to this defect of CT scans is to perform one or more pulmonarybiopsies in order to further examine the nature of the SPNs identifiedby the CT scans. Pulmonary biopsies, however, can be risky. Statisticsshow that one in four pulmonary biopsies results in pneumothorax, apunctured lung. Also, the elderly and patients on blood thinners are atsubstantial risk of bleeding during pulmonary biopsies. In addition,pulmonary biopsies are relatively expensive. These and other factorshave lead to search for alternative diagnostic methods to replacepulmonary biopsies.

The non-invasive optical probing techniques and devices described inthis application may be used to detect and diagnose lung diseases inhumans and animals including lung cancer. The optical probe headdescribed in various implementations may be inserted into the lung tooptically measure various parts of the lung without taking physicalsamples from the lung. The following sections first describe thespecific implementations of non-invasive optical probing based onspectral responses of tissues or parts and interactions of differentoptical modes in the probe light. Next, examples of integrated lungdisease diagnosis and treatment systems that combine CT scan withoptical probing and laser treatment are described.

Spectral responses of materials and substances are important in manyapplications. For example, some distinct material properties arereflected in their spectral responses and can be detected or measuredvia the spectral responses. A detected or measured distinct property maybe used for, e.g., identifying and locating a region or area such as abody part of a person or animal. Next, the identified body part may befurther analyzed. As a more specific example, cancer tumors or otherconditions can be detected and located using the measured spectralresponses. Various non-invasive optical techniques described in thisapplication may be used to measure spectral responses of a targeted bodypart of a person or animal. An optical probe head is used to scan aprobing beam through the body part to optically measure the opticalresponses of the targeted body part to obtain a map. At each locationwithin the targeted body part, light at different optical wavelengths isused to obtain optical absorption responses at these differentwavelengths. Notably, the spectral absorption features of a target layerunderneath the surface may be optically selected and measured byrejecting contributions to the reflected probe light made by the tissuesoutside the boundaries of the target layer.

In some implementations, a single broadband light source may be used forthe acquisition of the spectral information within the emission spectralrange of the light source. A tunable optical filter may be used tosingle out the spectral response of a narrow wavelength band within theemitted spectrum of the light source. When an absorbance feature to bemeasured or various targeted absorbance features in a body part undermeasured occupy a broad spectral range beyond the emission spectralbandwidth of a single light source, the light source may be implementedby combining two or more light sources for the acquisition of spectralabsorbance mapping (SAM) in tissues and other samples.

The following sections first describe various techniques and devices fornon-invasive optical probing using a single light source and thendescribe devices and techniques that combine two or more different lightsources at different spectral ranges for the SAM measurements.

Energy in light traveling in an optical path such as an opticalwaveguide may be in different propagation modes. Different propagationmodes may be in various forms. States of optical polarization of lightare examples of such propagation modes. Two independent propagationmodes do not mix with one another in the absence of a couplingmechanism. As an example, two orthogonally polarization modes do notinteract with each other even though the two modes propagate along thesame optical path or waveguide and are spatially overlap with eachother. The exemplary techniques and devices described in thisapplication use two independent propagation modes in light in the sameoptical path or waveguide to measure optical properties of a sample. Aprobe head may be used to direct the light to the sample, either in twopropagation modes or in a single propagation modes, and receive thereflected or back-scattered light from the sample.

For example, one beam of guided light in a first propagation mode may bedirected to a sample. A first portion of the first propagation mode maybe arranged to be reflected before reaching the sample while a secondportion in the first propagation mode is allowed to reach the sample.The reflection of the second portion from the sample is controlled in asecond propagation mode different from the first propagation mode toproduce a reflected second portion. Both the reflected first portion inthe first propagation mode and the reflected second portion in thesecond propagation mode are directed through a common waveguide into adetection module to extract information from the reflected secondportion on the sample.

In another example, optical radiation in both a first propagation modeand a second, different propagation mode may be guided through anoptical waveguide towards a sample. The radiation in the firstpropagation mode is directed away from the sample without reaching thesample. The radiation in the second propagation mode is directed tointeract with the sample to produce returned radiation from theinteraction. Both the returned radiation in the second propagation modeand the radiation in the first propagation mode are coupled into theoptical waveguide away from the sample. The returned radiation in thesecond propagation mode and the radiation in the first propagation modefrom the optical waveguide are then used to extract information of thesample.

In these and other implementations based on the disclosure of thisapplication, two independent modes are confined to travel in the samewaveguide or the same optical path in free space except for the extradistance traveled by the probing light between the probe head and thesample. This feature stabilizes the relative phase, or differentialoptical path, between the two modes of light, even in the presence ofmechanical movement of the waveguides. This is in contrast tointerferometer sensing devices in which sample light and reference lighttravel in different optical paths. These interferometer sensing deviceswith separate optical paths are prone to noise caused by the variationin the differential optical path, generally complex in opticalconfigurations, and difficult to operate and implement. The examplesdescribed below based on waveguides are in part designed to overcomethese and other limitations.

FIG. 2 shows one example of a sensing device according to oneimplementation. This device directs light in two propagation modes alongthe same waveguide to an optical probe head near a sample 205 foracquiring information of optical inhomogeneity in the sample. A sampleholder may be used to support the sample 205 in some applications. Lightradiation from a broadband light source 201 is coupled into the firstdual-mode waveguide 271 to excite two orthogonal propagation modes, 001and 002. A light director 210 is used to direct the two modes to thesecond dual-mode waveguide 272 that is terminated by a probe head 220.The probe head 220 may be configured to perform at least the followingfunctions. The first function of the probe head 220 is to reverse thepropagation direction of a portion of light in the waveguide 272 in themode 001; the second function of the probe head 220 is to reshape anddeliver the remaining portion of the light in mode 002 to the sample205; and the third function of the probe head 220 is to collect thelight reflected from the sample 205 back to the second dual-modewaveguide 272. The back traveling light in both modes 001 and 002 isthen directed by light director 210 to the third waveguide 273 andfurther propagates towards a differential delay modulator 250. Thedifferential delay modulator 250 is capable of varying the relativeoptical path length and optical phase between the two modes 001 and 002.A detection subsystem 260 is used to superpose the two propagation modes001 and 002 to form two new modes, mutually orthogonal, to be receivedby photo-detectors. Each new mode is a mixture of the modes 001 and 002.

The superposition of the two modes 001 and 002 in the detectionsubsystem 260 allows for a range detection. The light entering thedetection subsystem 260 in the mode 002 is reflected by the sample,bearing information about the optical inhomogeneity of the sample 205,while the other mode, 001, bypassing the sample 205 inside probe head220. So long as these two modes 001 and 002 remain independent throughthe waveguides their superposition in the detection subsystem 260 may beused to obtain information about the sample 205 without the separateoptical paths used in some conventional Michelson interferometersystems.

For the simplicity of the analysis, consider a thin slice of the sourcespectrum by assuming that the amplitude of the mode 001 is E₀₀₁ in afirst linear polarization and that of the mode 002 is E₀₀₂ in a second,orthogonal linear polarization in the first waveguide 271. The sample205 can be characterized by an effective reflection coefficient r thatis complex in nature; the differential delay modulator 250 can becharacterized by a pure phase shift Γ exerted on the mode 001. Let usnow superpose the two modes 001 and 002 by projecting them onto a pairof new modes, E_(A) and E_(B), by a relative 45-degree rotation in thevector space. The new modes, E_(A) and E_(B), may be expressed asfollowing:

$\begin{matrix}\left\{ \begin{matrix}{{E_{A} = {\frac{1}{\sqrt{2}}\left( {{{\mathbb{e}}^{j\Gamma}E_{001}} + {rE}_{002}} \right)}};} \\{E_{B} = {\frac{1}{\sqrt{2}}{\left( {{{\mathbb{e}}^{j\Gamma}E_{001}} + {rE}_{002}} \right).}}}\end{matrix} \right. & (1)\end{matrix}$It is assumed that all components in the system, except for the sample205, are lossless. The resultant intensities of the two superposed modesare

$\begin{matrix}\left\{ \begin{matrix}{{I_{A} = {\frac{1}{2}\left\lbrack {E_{001}^{2} + E_{002}^{2} + {{r}E_{001}E_{002}{\cos\left( {\Gamma - \varphi} \right)}}} \right\rbrack}};} \\{{I_{B} = {\frac{1}{2}\left\lbrack {E_{001}^{2} + E_{002}^{2} - {{r}E_{001}E_{002}{\cos\left( {\Gamma - \varphi} \right)}}} \right\rbrack}},}\end{matrix} \right. & (2)\end{matrix}$where φ is the phase delay associated with the reflection from thesample. A convenient way to characterize the reflection coefficient r isto measure the difference of the above two intensities, i.e.I _(A) −I _(B) =|r|E ₀₀₁ E ₀₀₂ cos(Γ−φ).  (3)If Γ is modulated by the differential delay modulator 250, the measuredsignal, Eq. (3), is modulated accordingly. For either a periodic or atime-linear variation of Γ, the measured signal responds with a periodicoscillation and its peak-to-peak value is proportional to the absolutevalue of r.

For a broadband light source 201 in FIG. 2, consider the two phases, Γand φ to be dependent on wavelength. If the two modes 001 and 002experience significantly different path lengths when they reach thedetection system 260, the overall phase angle, Γ−φ, should besignificantly wavelength dependant as well. Consequently the measuredsignal, being an integration of Eq. (3) over the source spectrum, yieldsa smooth function even though Γ is being varied. The condition for asignificant oscillation to occur in the measured signal is when the twomodes 001 and 002 experience similar path lengths at the location oftheir superposition. In this case the overall phase angle, Γ−φ, becomeswavelength independent or nearly wavelength independent. In other words,for a given relative path length set by the modulator 250, anoscillation in the measured signal indicates a reflection, in the othermode, from a distance that equalizes the optical path lengths traveledby the two modes 001 and 002. Therefore the system depicted in FIG. 2can be utilized for ranging reflection sources.

Due to the stability of the relative phase between the two modes, 001and 002, phase-sensitive measurements can be performed with the systemin FIG. 2 with relative ease. The following describes an exemplarymethod based on the system in FIG. 2 for the determination of theabsolute phase associated with the radiation reflected from the sample205.

In this method, a sinusoidal modulation is applied to the differentialphase by the differential delay modulator 250, with a modulationmagnitude of M and a modulation frequency of Ω. The difference inintensity of the two new modes is the measured and can be expressed asfollows:I _(A) −I _(B) =|r|E ₀₀₁ E ₀₀₂ cos [M sin(Ωt)−φ].  (4)It is clear from Eq. (4) that the measured exhibits an oscillation at abase frequency of Ω and oscillations at harmonic frequencies of the basefrequency Ω. The amplitudes of the base frequency and each of theharmonics are related to φ and |r|. The relationships between r and theharmonics can be derived. For instance, the amplitude of thebase-frequency oscillation and the second harmonic can be found from Eq.(4) to be:A _(Ω) =E ₀₀₁ E ₀₀₂ J ₁(M)|r| sin φ;  (5a)A _(2Ω) =E ₀₀₁ E ₀₀₂ J ₂(M)|r| cos φ,  (5b)where J₁ and J₂ are Bessel functions of the first and second order,respectively. Eq. (5a) and (5b) can be used to solve for |r| and φ, i.e.the complete characterization of r. We can therefore completelycharacterize the complex reflection coefficient r by analyzing theharmonic content of various orders in the measured signal. Inparticular, the presence of the base-frequency component in the measuredis due to the presence of φ.

FIG. 3 shows an exemplary implementation of the system depicted in FIG.2. The spectrum of source 201 may be chosen to satisfy the desiredranging resolution. The broader the spectrum is the better the rangingresolution. Various light sources may be used as the source 201. Forexample, some semiconductor superluminescent light emitting diodes(SLED) and amplified spontaneous emission (ASE) sources may possess theappropriate spectral properties for the purpose. In this particularexample, a polarization controller 302 may be used to control the stateof polarization in order to proportion the magnitudes of the two modes,001 and 002, in the input waveguide 371. The waveguide 371 and otherwaveguides 372 and 373 may be dual-mode waveguides and are capable ofsupporting two independent polarization modes which are mutuallyorthogonal. One kind of practical and commercially available waveguideis the polarization maintaining (PM) optical fiber. A polarizationmaintaining fiber can carry two independent polarization modes, namely,the s-wave polarized along its slow axis and the p-wave polarized alongits fast axis. In good quality polarization maintaining fibers these twomodes can have virtually no energy exchange, or coupling, forsubstantial distances. Polarization preserving circulator 310 directsthe flow of optical waves according to the following scheme: the twoincoming polarization modes from fiber 371 are directed into the fiber372; the two incoming polarization modes from fiber 372 are directed tothe fiber 373. A polarization-preserving circulator 310 may be used tomaintain the separation of the two independent polarization modes. Forinstance, the s-wave in the fiber 371 should be directed to the fiber372 as s-wave or p-wave only. Certain commercially availablepolarization-preserving circulators are adequate for the purpose.

The system in FIG. 3 implements an optical probe head 320 coupled to thewaveguide 372 for optically probing the sample 205. The probe head 320delivers a portion of light received from the waveguide 372, the lightin one mode (e.g., 002) of the two modes 001 and 002, to the sample 205and collects reflected and back-scattered light in the same mode 002from the sample 205. The returned light in the mode 002 collected fromthe sample 205 carries information of the sample 205 and is processed toextract the information of the sample 205. The light in the other mode001 in the waveguide 372 propagating towards the probe head 320 isreflected back by the probe head 320. Both the returned light in themode 002 and the reflected light in the mode 001 are directed back bythe probe head 320 into the waveguide 372 and to the differential delaymodulator 250 and the detection system 260 through the circulator 310and the waveguide 373.

In the illustrated implementation, the probe head 320 includes a lenssystem 321 and a polarization-selective reflector (PSR) 322. The lenssystem 321 is to concentrate the light energy into a small area,facilitating spatially resolved studies of the sample in a lateraldirection. The polarization-selective reflector 322 reflects the mode001 back and transmits the mode 002. Hence, the light in the mode 002transmits through the probe head 320 to impinge on the sample 205. Backreflected or scattered the light from the sample 205 is collected by thelens system 321 to propagate towards the circulator 310 along with thelight in the mode 001 reflected by PSR 322 in the waveguide 372.

FIG. 4 shows details of the probe head 320 and an example of thepolarization-selective reflector (PSR) 322 according to oneimplementation. The PSR 322 includes a polarizing beam splitter (PBS)423 and a reflector or mirror 424 in a configuration as illustratedwhere the PBS 423 transmits the selected mode (e.g., mode 002) to thesample 205 and reflects and diverts the other mode (e.g., mode 001) awayfrom the sample 205 and to the reflector 424. By retro reflection of thereflector 424, the reflected mode 001 is directed back to the PBS 423and the lens system 321. The reflector 424 may be a reflective coatingon one side of beam splitter 423. The reflector 424 should be aligned toallow the reflected radiation to re-enter the polarization-maintainingfiber 372. The transmitted light in the mode 002 impinges the sample 205and the light reflected and back scattered by the sample 205 in the mode002 transmits through the PBS 423 to the lens system 321. The lenssystem 321 couples the light in both the modes 001 and 002 into thefiber 372.

In the implementation illustrated in FIG. 3, the detection system 260includes a polarizing beam splitter 361, and two photodetectors 362 and363. The polarizing beam splitter 361 is used to receive the twoindependent polarization modes 001 and 002 from the modulator 250 andsuperposes the two independent polarization modes 001 and 002. The beamsplitter 361 may be oriented in such a way that, each independentpolarization is split into two parts and, for each independentpolarization mode, the two split portions possess the same amplitude.This way, a portion of the mode 001 and a portion of the mode 002 arecombined and mixed in each of the two output ports of the beam splitter361 to form a superposed new mode and each photodetector receives asuperposed mode characterized by Eq. (1). The polarizing beam splitter361 may be oriented so that the incident plane of its reflection surfacemakes a 45-degree angle with one of the two independent polarizationmode, 001 or 002.

The system in FIG. 3 further implements an electronic controller orcontrol electronics 370 to receive and process the detector outputs fromthe photodetectors 362 and 363 and to control operations of the systems.The electronic controller 370, for example, may be used to control theprobe head 320 and the differential delay modulator 250. Differentialdelay modulator 250, under the control of the electronics and programs,generates a form of differential phase modulation as the differentialpath length scans through a range that matches a range of depth insidethe sample 205. The electronic controller 370 may also be programmed torecord and extract the amplitude of the oscillation in the measuredsignal characterized by Eq. (3) at various differential path lengthsgenerated by the modulator 250. Accordingly, a profile of reflection asa function of the depth can be obtained as a one-dimensionalrepresentation of the sample inhomogeneity at a selected location on thesample 205.

For acquiring two-dimensional images of optical inhomogeneity in thesample 205, the probe head 320 may be controlled via a position scannersuch as a translation stage or a piezo-electric positioner so that theprobing light scans in a lateral direction, perpendicular to the lightpropagation direction. For every increment of the lateral scan a profileof reflection as a function of depth can be recorded with the methoddescribed above. The collected information can then be displayed on adisplay and interface module 372 to form a cross-sectional image thatreveals the inhomogeneity of the sample 205.

In general, a lateral scanning mechanism may be implemented in eachdevice described in this application to change the relative lateralposition of the optical probe head and the sample to obtain a2-dimensional map of the sample. A xy-scanner, for example, may beengaged either to the optical head or to a sample holder that holds thesample to effectuate this scanning in response to a position controlsignal generated from the electronic controller 370.

FIGS. 5A and 5B illustrate another exemplary system that use waveguides271, 272, and 273 and a light director 210 to direct light in two modesto and from the probe head 320 in measuring the sample 205. A firstoptical polarizer 510 is oriented with respect to the polarization axesof the PM waveguide 271 to couple radiation from the broadband lightsource 201 into the waveguide 271 in two orthogonal linear polarizationmodes as the independent propagation modes. An optical phase modulator520 is coupled in the waveguide 271 to modulate the optical phase oflight in one guided mode relative to the other. A variable differentialgroup delay (VDGD) device 530 is inserted in or connected to thewaveguide 273 to introduce a controllable amount of optical pathdifference between the two waves. A second optical polarizer 540 and anoptical detector 550 are used here to form a detection system. Thesecond polarizer 540 is oriented to project both of the guided wavesonto the same polarization direction so that the changes in optical pathdifference and the optical phase difference between the two propagationmodes cause intensity variations, detectable by the detector 550.

The light from the source 201 is typically partially polarized. Thepolarizer 510 may be aligned so that maximum amount of light from thesource 201 is transmitted and that the transmitted light is coupled toboth of the guided modes in the waveguide 271 with the substantiallyequal amplitudes. The electric fields for the two orthogonalpolarization modes S and P in the waveguide 271 can be expressed as:

$\begin{matrix}\left\{ \begin{matrix}{{E_{s} = {\frac{1}{\sqrt{2}}E}},} \\{E_{p} = {\frac{1}{\sqrt{2}}{E.}}}\end{matrix} \right. & (6)\end{matrix}$where the electric field transmitting the polarizer is denoted as E. Itshould be appreciated that the light has a finite spectral width(broadband or partially coherent). The fields can be described by thefollowing Fourier integral:E=∫E _(ω) e ^(jωt) dω.  (7)For the simplicity of the analysis, a thin slice of the spectrum, i.e. alightwave of a specific wavelength, is considered below. Without loosinggenerality, it is assumed that all the components, including polarizers,waveguides, Router, PSR and VDGD, are lossless. Let us designate thereflection coefficient of the sample r, that is complex in nature. Thep-wave picks up an optical phase, Γ, relative to the s-wave as theyreach the second polarizer 540:

$\begin{matrix}\left\{ \begin{matrix}{{E_{s} = {\frac{1}{\sqrt{2}}E}},} \\{E_{p} = {\frac{1}{\sqrt{2}}{{rE\mathbb{e}}^{j\Gamma}.}}}\end{matrix} \right. & (8)\end{matrix}$The light that passes through Polarizer 540 can be expressed by

$\begin{matrix}{E_{a} = {{\frac{1}{\sqrt{2}}\left( {E_{s} + E_{p}} \right)} = {\frac{1}{2}{{E\left( {1 + {r\mathbb{e}}^{j\;\Gamma}} \right)}.}}}} & (9)\end{matrix}$The intensity of the light that impinges on the photodetector 550 isgiven by:

$\begin{matrix}{I = {{E_{a}E_{a}^{*}} = {\frac{1}{4}{{{E}^{2}\left\lbrack {1 + {r}^{2} + {2{r}{\cos\left( {\Gamma + \delta} \right)}}} \right\rbrack}.}}}} & (10)\end{matrix}$where phase angle δ reflects the complex nature of the reflectioncoefficient of the sample 205 and is defined byr=|r|e ^(jδ).  (11)Assuming the modulator 520 exerts a sinusoidal phase modulation, withmagnitude M and frequency Ω, in the p-wave with respect to the s-wave,the light intensity received by the detector 550 can be expressed asfollows:

$\begin{matrix}{I = {{\frac{1 + {r}^{2}}{4}{E}^{2}} + {\frac{r}{2}{E}^{2}{{\cos\left\lbrack {{M\;{\sin\left( {\Omega\; t} \right)}} + \varphi + \delta} \right\rbrack}.}}}} & (12)\end{matrix}$where phase angle φ is the accumulated phase slip between the two modes,not including the periodic modulation due to the modulator 520. The VDGD530 or a static phase shift in the modulator 520, may be used to adjustthe phase difference between the two modes to eliminate φ.

FIG. 6 illustrates the waveform of the intensity I received at thedetector 550 as a function of the phase. The detected light intensityexhibits an oscillating waveform that possesses a base frequency of Ωand its harmonics. The amplitudes of the base frequency and each of theharmonics are related to δ and |r|. The mathematical expressions for therelationships between r and the harmonics can be derived. For instance,the amplitude of the base-frequency oscillation and the second harmonicare found to be:A _(Ω)=0.5|E| ² J ₁(M)|r| sin δ;  (13a)A _(2Ω)=0.5|E| ² J ₂(M)|r| cos δ,  (13b)where J₁ and J₂ are Bessel functions of the first and second order,respectively. Eq. (13a) and (13b) can be used to solve for |r| and δ,i.e. the complete characterization of r.

The effect of having a broadband light source 201 in the system in FIGS.5A and 5B is analyzed below. When there is a significant differentialgroup delay between the two propagation modes there must be anassociated large phase slippage φ that is wavelength dependent. Asubstantial wavelength spread in the light source means that the phaseslippage also possesses a substantial spread. Such a phase spread cannotbe eliminated by a phase control device that does not also eliminate thedifferential group delay. In this case the detected light intensity isgiven by the following integral:

$\begin{matrix}{I = {\int\left\{ {{\frac{1 + {r}^{2}}{4}{{E(\lambda)}}^{2}} + {\frac{r}{2}{{E(\lambda)}}^{2}{\cos\left\lbrack {{M\;{\sin\left( {\Omega\; t} \right)}} + {\varphi(\lambda)} + \delta} \right\rbrack}{{\mathbb{d}\lambda}.}}} \right.}} & (14)\end{matrix}$It is easy to see that if the range of φ(λ) is comparable to π for thebandwidth of the light source no oscillation in I can be observed asoscillations for different wavelengths cancel out because of their phasedifference. This phenomenon is in close analogy to the interference ofwhite light wherein color fringes are visible only when the pathdifference is small (the film is thin). The above analysis demonstratesthat the use of a broadband light source enables range detection usingthe proposed apparatus. In order to do so, let the s-wave to have alonger optical path in the system compared to the p-wave (not includingits round-trip between Probing Head and Sample). For any given pathlength difference in the system there is a matching distance betweenProbing Head and Sample, z, that cancels out the path length difference.If an oscillation in I is observed the p-wave must be reflected fromthis specific distance z. By varying the path length difference in thesystem and record the oscillation waveforms we can therefore acquire thereflection coefficient r as a function of the longitudinal distance z,or depth. By moving Probing Head laterally, we can also record thevariation of r in the lateral directions.

FIG. 7 further shows one exemplary operation of the described system inFIG. 5B or the system in FIG. 3 for acquiring images of opticalinhomogeneity. At step 710, the relative phase delay between the twomodes is changed, e.g., increased by an increment, to a fixed value formeasuring the sample 205 at a corresponding depth. This may beaccomplished in FIG. 5B by using the differential delay device 530 orthe bias in the differential delay modulator 250 in FIG. 3. At step 720,a modulation driving signal is sent to the modulator 520 in FIG. 5B orthe modulator 250 in FIG. 3 to modulate the relative phase delay betweenthe two modes around the fixed value. At step 730, the intensitywaveform received in the detector 550 in FIG. 5B or the intensitywaveforms received in the detectors 362,363 in FIG. 3 are measured andstored in the electronic controller 370. Upon completion of the step730, the electronic controller 370 controls the differential delaydevice 530 in FIG. 5B or the bias in the differential delay modulator250 in FIG. 3 to change the relative phase delay between the two modesto a different fixed value for measuring the sample 205 at a differentdepth. This process iterates as indicated by the processing loop 740until desired measurements of the sample at different depths at the samelocation are completed. At this point, electronic controller 370controls the probe head 320 to laterally move to a new location on thesample 205 and repeat the above measurements again until all desiredlocations on the sample 205 are completed. This operation is representedby the processing loop 750. The electronic controller 370 processes eachmeasurement to compute the values of δ and |r| from the base oscillationand the harmonics at step 760. Such data processing may be performedafter each measurement or after all measurements are completed. At step770, the computed data is sent to the display module 372.

In the above implementations, light for sensing the sample 205 is notseparated into two parts that travel along two different optical paths.Two independent propagation modes of the light are guided essentially inthe same waveguide at every location along the optical path except forthe extra distance traveled by one mode between the probe head 320 andthe sample 205. After redirected by the probe head 320, the two modesare continuously guided in the same waveguide at every location alongthe optical path to the detection module.

Alternatively, the light from the light source to the probe head may becontrolled in a single propagation mode (e.g., a first propagation mode)rather than two different modes. The probe head may be designed to causea first portion of the first mode to reverse its propagation directionwhile directing the remaining portion, or a second portion, to reach thesample. The reflection or back scattered light of the second portionfrom the sample is collected by the probe head and is controlled in thesecond propagation mode different from the first mode to produce areflected second portion. Both the reflected first portion in the firstpropagation mode and the reflected second portion in the secondpropagation mode are directed by the probe head through a commonwaveguide into the detection module for processing. In comparison withthe implementations that use light in two modes throughout the system,this alternative design further improves the stability of the relativephase delay between the two modes at the detection module and providesadditional implementation benefits.

FIGS. 8A and 8B illustrate one exemplary design of the optical layout ofthe optical sensing system and its system implementation with anelectronic controller. An input waveguide 871 is provided to directlight in a first propagation mode, e.g., the mode 001, from thebroadband light source 201 to a light director 810. The waveguide 871may be a mode maintaining waveguide designed to support at least onepropagation mode such as the mode 001 or 002. When light is coupled intothe waveguide 871 in a particular mode such as the mode 001, thewaveguide 871 essentially maintains the light in the mode 001. Apolarization maintaining fiber supporting two orthogonal linearpolarization modes, for example, may be used as the waveguide 871.Similar to systems shown in FIGS. 2, 3, 5A and 5B, dual-mode waveguides272 and 273 are used to direct the light. A light director 510 is usedto couple the waveguides 871, 272, and 273, to convey the mode 001 fromthe input waveguide 871 to one of the two modes (e.g., modes 001 and002) supported by the dual-mode waveguide 272, and to direct light intwo modes from the waveguide 272 to the dual-mode waveguide 273. In theexample illustrated in FIG. 8A, the light director 810 couples the lightin the mode 001 from the waveguide 871 into the same mode 001 in thewaveguide 272. Alternatively, the light director 810 may couple thelight in the mode 001 from the waveguide 871 into the different mode 002in the waveguide 272. The dual-mode waveguide 271 is terminated at theother end by a probe head 820 which couples a portion of light to thesample 205 for sensing.

The probe head 820 is designed differently from the prove head 320 inthat the probe head 830 converts part of light in the mode 001 into theother different mode 002 when the light is reflected or scattered backfrom the sample 205. Alternatively, if the light in the waveguide 272that is coupled from the waveguide 871 is in the mode 002, the probehead 820 converts that part of light in the mode 002 into the otherdifferent mode 001 when the light is reflected or scattered back fromthe sample 205. In the illustrated example, the probe head 820 performsthese functions: a) to reverse the propagation direction of a smallportion of the incoming radiation in mode 001; b) to reshape theremaining radiation and transmit it to the sample 205; and c) to convertthe radiation reflected from the sample 205 to an independent mode 002supported by the dual-mode waveguide 272. Since the probe head 820 onlyconverts part of the light into the other mode supported by thewaveguide 272, the probe head 820 is a partial mode converter in thisregard. Due to the operations of the probe head 820, there are two modespropagating away from the probe head 820, the mode 001 that bypasses thesample 205 and the mode 002 for light that originates from samplereflection or back scattering. From this point on, the structure andoperations of the rest of the system shown in FIG. 8A may be similar tothe systems in FIGS. 2, 3, 5A, and 5B.

FIG. 8B shows an exemplary implementation of the design in FIG. 8A wherean electronic controller 2970 is used to control the differential delaymodulator 250 and the probe head 820 and a display and interface module372 is provided. Radiation from broadband light source 201, which may bepartially polarized, is further polarized and controlled by an inputpolarization controller 802 so that only a single polarization mode isexcited in polarization-maintaining fiber 371 as the waveguide 871 inFIG. 8A. a polarization preserving circulator may be used to implementthe light director 810 for routing light from the waveguide 371 to thewaveguide 372 and from the waveguide 372 to the waveguide 373.

The probe head 820 in FIG. 8B may be designed to include a lens system821 similar to the lens system 321, a partial reflector 822, and apolarization rotator 823. The partial reflector 822 is used to reflectthe first portion of light received from the waveguide 372 back to thewaveguide 372 without changing its propagation mode and transmits lightto and from the sample 205. The polarization rotator 823 is used tocontrol the light from the sample 205 to be in the mode 002 upon entryof the waveguide 372.

FIG. 9 shows another example of a system implementation where theoptical probe head 820 receives light in a single input mode andconverts part of light into a different mode. An input polarizer 510 isused in the input PM fiber 272 to control the input light in the singlepolarization mode. A phase modulator 520 and a variable differentialgroup delay device 530 are coupled to the output PM fiver 273 to controland modulate the relative phase delay of the two modes before opticaldetection. An output polarizer 540 is provided to mix the two modes andthe detector 550 is used to detect the output from the output polarizer540.

FIGS. 10A and 10B show two examples of the possible designs for theprobe head 820 including a partially reflective surface 1010, a lenssystem 1020, and a quarter-wave plate 1030 for rotating the polarizationand to convert the mode. In FIG. 10A, the termination or end facet ofpolarization-maintaining fiber 372 is used as the partial reflector1010. An uncoated termination of an optical fiber reflects approximately4% of the light energy. Coatings can be used to alter the reflectivityof the termination to a desirable value. The lens system 1020 reshapesand delivers the remaining radiation to sample 205. The other roleplayed by the lens system 1020 is to collect the radiation reflectedfrom the sample 205 back into the polarization-maintaining fiber 372.The quarter wave plate 1030 is oriented so that its optical axis make a45-degree angle with the polarization direction of the transmittedlight. Reflected light from the sample 205 propagates through thequarter wave plate 1030 once again to become polarized in a directionperpendicular to mode 001, i.e. mode 002. Alternatively, the quarterwave plate 1030 may be replaced by a Faraday rotator. The head design inFIG. 10B changes the positions of the lens system 1020 and the quarterwave plate or Faraday rotator 1030.

In the examples in FIGS. 8A, 8B, and 9, there is only one polarizationmode entering the light director 810 or the polarization-preservingcirculator from waveguide 871 or 371. Therefore, the light director 810or the polarization preserving circulator may be constructed with apolarization-maintaining optical circulator 1110 and two polarizationbeam splitters 1120 and 1130 as shown in FIG. 11. Thepolarization-maintaining circulator 1110 is used to convey only onepolarization mode among its three ports, rather than both modes as inthe case shown in FIGS. 3, 5A and 5B. The polarizing beam splitter 1120and 1130 are coupled to polarization-maintaining circulator 1110 so thatboth polarization modes entering Port 2 are conveyed to Port 3 andremain independent.

A number of hardware choices are available for differential delaymodulator 250. FIG. 12 illustrates the general design of the modulator250 where an external control signal is applied to control adifferential delay element to change and modulate the relative delay inthe output. Either mechanical or non-mechanical elements may be used toproduce the desired relative delay between the two modes and themodulation on the delay.

In one implementation, a non-mechanical design may include one or moresegments of tunable birefringent materials such as liquid crystalmaterials or electro-optic birefringent materials such as lithiumniobate crystals in conjunction with one or more fixed birefringentmaterials such as quartz and rutile. The fixed birefringent materialprovides a fixed delay between two modes and the tunable birefringentmaterial provides the tuning and modulation functions in the relativedelay between the two modes. FIG. 12A illustrates an example of thisnon-mechanical design where the two modes are not physically separatedand are directed through the same optical path with birefringentsegments which alter the relative delay between two polarization modes.

FIG. 12B shows a different design where the two modes in the receivedlight are separated by a mode splitter into two different optical paths.A variable delay element is inserted in one optical path to adjust andmodulate the relative delay in response to an external control signal. Amode combiner is then used to combine the two modes together in theoutput. The mode splitter and the mode combiner may be polarizationbeams splitters when two orthogonal linear polarizations are used as thetwo modes.

The variable delay element in one of the two optical paths may beimplemented in various configurations. For example, the variable delayelement may be a mechanical element. A mechanical implementation of thedevice in FIG. 12B may be constructed by first separating the radiationby polarization modes with a polarizing beam splitter, one polarizationmode propagating through a fixed optical path while the otherpropagating through a variable optical path having a piezoelectricstretcher of polarization maintaining fibers, or a pair of collimatorsboth facing a mechanically movable retroreflector in such a way that thelight from one collimator is collected by the other through a trip toand from the retroreflector, or a pair collimators optically linkedthrough double passing a rotatable optical plate and bouncing off areflector.

FIGS. 13A and 13B illustrate two examples of a mechanical variable delayelement suitable for FIG. 12B. Such a mechanical variable delay devicemay be used to change the optical path length of a light beam at highspeeds and may have various applications other than what is illustratedin FIG. 12B. In addition, the optical systems in this application mayuse such a delay device.

The mechanical delay device shown in FIG. 13A includes an optical beamsplitter 1310, a rotating optical plate 1320 which may be a transparentplate, and a mirror or reflector 1330. The beam splitter 1310 is used asthe input port and the output port for the device. The rotating opticalplate 1320 is placed between the mirror 1330 and the beam splitter 1310.The input light beam 1300 is received by the beam splitter 1310 alongthe optical path directing from the beam splitter 1310 to the mirror1330 through the rotating optical plate 1320. A portion of the light1300 transmitting through the beam splitter 1310 is the beam 1301 whichimpinges on and transmits through the rotating optical plate 1320. Themirror or other optical reflector 1330 is oriented to be perpendicularto the light beam incident to the optical plate 1310 from the oppositeside. The reflected light beam 1302 from the mirror 1320 traces the sameoptical path back traveling until it encounters the Beam Splitter 1310.The Beam Splitter 1310 deflects part of the back traveling light 1302 toa different direction as the output beam 1303.

In this device, the variation of the optical path length is caused bythe rotation of the Optical Plate 1320. The Optical Plate 1320 may bemade of a good quality optical material. The two optical surfaces may beflat and well polished to minimize distortion to the light beam. Inaddition, the two surfaces should be parallel to each other so that thelight propagation directions on both sides of the Optical Plate 1320 areparallel. The thickness of the Optical Plate 1320 may be chosenaccording to the desirable delay variation and the range of the rotationangle. The optical path length experienced by the light beam isdetermined by the rotation angle of the Optical Plate 1320. When thesurfaces of the Optical Plate 1320 is perpendicular to the light beam(incident angle is zero), the path length is at its minimum. The pathlength increases as the incident angle increases.

In FIG. 13A, it may be beneficial to collimate the input light beam sothat it can travel the entire optical path without significantdivergence. The Optical Plate 1320 may be mounted on a motor forperiodic variation of the optical delay. A good quality mirror with aflat reflecting surface should be used to implement the mirror 1330. Thereflecting surface of the mirror 1330 may be maintained to beperpendicular to the light beam.

If a linearly polarized light is used as the input beam 1300 in FIG.13A, it is beneficial to have the polarization direction of the lightparallel to the incident plane (in the plane of the paper) as lessreflection occurs at the surfaces of Optical Plate 1320 for thispolarization compared to other polarization directions. Antireflectioncoatings can be used to further reduce the light reflection on thesurfaces of the Optical Plate 1320.

The beam splitter 1310 used in FIG. 13A uses both its opticaltransmission and optical reflection to direct light. This aspect of thebeam splitter 1310 causes reflection loss in the output of the devicedue to the reflection loss when the input light 1300 first enters thedevice through transmission of the beam splitter 1310 and thetransmission loss when the light exits the device through reflection ofthe beam splitter 1310. For example, a maximum of 25% of the total inputlight may be left in the output light if the beam splitter is a 50/50beam splitter. To avoid such optical loss, an optical circulator may beused in place of the beam splitter 1320. FIG. 13B illustrates an examplewhere the optical circulator 1340 with 3 ports is used to direct inputlight to the optical plate 1320 and the mirror 1330 and directs returnedlight to the output port. The optical circulator 1340 may be designed todirect nearly all light entering its port 1 to port 2 and nearly alllight entering its port 2 to the port 3 with nominal optical loss andhence significantly reduces the optical loss in the device. Commerciallyavailable optical circulators, either free-space or fiber-based, may beused to implement the circulator 1340.

FIG. 14A shows an exemplary implementation of the delay device in FIG.12B as part of or the entire differential delay modulator 250. A firstoptical mode splitter 1410 is used to separate two modes in thewaveguide 373 into two paths having two mirrors 1431 and 1432,respectively. A second optical mode splitter 1440, which is operated asa mode combiner, is used to combine the two modes into an output. If thetwo modes are two orthogonal linear polarizations, for example,polarization beam splitters may be used to implement the 1410 and 1440.A variable optical delay line or device 1420 is placed in the upper pathto control the differential delay between the two paths. The output maybe coupled into another dual-mode waveguide 1450 leading to thedetection module or directly sent into the detection module. FIG. 14Bshows a delay device based on the design in FIG. 14A where the mirror1432 and the variable optical delay line 1420 are implemented by themechanical delay device in FIG. 13A. The mechanical delay device in FIG.13B may also be used to implement the device in FIG. 14A.

In the above examples, a single dual-mode waveguide 272 or 372 is usedas an input and output waveguide for the probe head 220, 320, or 820.Hence, the input light, either in a single mode or two independentmodes, is directed into the probe head through that dual-mode waveguide272 or 372, and the output light in the two independent modes is alsodirected from the probe head to the detection subsystem or detector.

Alternatively, the single dual-mode waveguide 272 or 372 may be replacedby two separate waveguides, one to direct input light from the lightsource to the probe head and another to direct light from the probe headto the detection subsystem or detector. As an example, the device inFIG. 2 may have a second waveguide different from the waveguide 272 todirect reflected light in two different modes from the optical probehead 220 to the modulator 250 and the detection subsystem 260. In thisdesign, the light director 210 may be eliminated. This may be anadvantage. In implementation, the optics within the probe head may bedesigned to direct the reflected light in two modes to the secondwaveguide.

FIG. 15 illustrates an example for this design as an alternative to thedevice shown in FIG. 5B. In this design, the probing light is deliveredto the sample 205 through one dual-mode waveguide 1510 and thereflected/scattered light is collected by the probe head 320 and isdirected through another dual-mode waveguide 1520. With the probe headshown in FIG. 4, the mirror 424 may be oriented and aligned so that thelight is reflected into the waveguide 1520 instead of the waveguide1510. This design may be applied to other devices based on thedisclosure of this application, including the exemplary devices in FIGS.2, 3, 8A, 8B and 9.

The above-described devices and techniques may be used to obtain opticalmeasurements of a given location of the sample at different depths bycontrolling the relative phase delay between two modes at differentvalues and optical measurements of different locations of the sample toget a tomographic map of the sample at a given depth or various depthsby laterally changing the relative position of the probe head over thesample. Such devices and techniques may be further used to perform othermeasurements on a sample, including spectral selective measurements on alayer of a sample.

In various applications, it may be beneficial to obtain informationabout certain substances, identifiable through their spectralabsorbance, dispersed in the samples. For this purpose, a tunablebandpass filter may be used to either filter the light incident to theprobe head to select a desired spectral window within the broadbandspectrum of the incident light to measure the response of the sample andto vary the center wavelength of the spectral window to measure aspectral distribution of the responses of the sample. This tuning of thebandpass filter allows a variable portion of the source spectrum to passwhile measuring the distribution of the complex reflection coefficientof the sample.

Alternatively, the broadband light may be sent to the optical probe headwithout optical filtering and the spectral components at differentwavelengths in the output light from the probe head may be selected andmeasured to measure the response of the sample around a selectedwavelength or the spectral distribution of the responses of the sample.In one implementation, a tunable optical bandpass filter may be insertedin the optical path of the output light from the probe head to filterthe light. In another implementation, a grating or other diffractiveoptical element may be used to optically separate different spectralcomponents in the output light to be measured by the detection subsystemor the detector.

As an example, FIG. 16 shows a system based on the design in FIG. 2where a tunable filter 1610 is inserted in the input waveguide 271 tofilter the input light in two different modes. FIG. 17 shows anotherexemplary system based on the design in FIG. 8A where a tunable filter1710 is inserted in the input waveguide 871 to filter the input light ina single mode. Such a tunable filter may be placed in other locations.

FIG. 18 illustrates the operation of the tunable bandpass filter in thedevices in FIGS. 16 and 17. The filter selects a narrow spectral bandwithin the spectrum of the light source to measure the spectral featureof the sample.

Notably, the devices and techniques of this application may be used toselect a layer within a sample to measure by properly processing themeasured data. Referring back to the devices in FIGS. 16 and 17, let usassume that the absorption characteristics of a layer bounded byinterfaces I and II is to be measured. For the simplicity ofdescription, it is assumed that the spectral absorption of the substancein the layer is characterized by a wavelength-dependent attenuationcoefficient μ_(h)(λ) and that of other volume is characterized byμ_(g)(λ). It is further assumed that the substance in the vicinity ofinterface I (II) possesses an effective and wavelength independentreflection coefficient r_(I) (r_(II)). If the characteristic absorptionof interest is covered by the spectrum of the light source, an opticalfilter 1610 or 1710 with a bass band tunable across the characteristicabsorption of the sample 205 may be used to measure the spectralresponses of the sample 205 centered at different wavelengths.

In operation, the following steps may be performed. First, thedifferential delay modulator 250 is adjusted so that the path lengthtraveled by one mode (e.g., the mode 001) matches that of radiationreflected from interface I in the other mode (e.g., the mode 002). Atthis point, the pass band of filter 1610 or 1710 may be scanned whilerecording the oscillation of the measured signal due to a periodicdifferential phase generated by the modulator 250. The oscillationamplitude as a function of wavelength is given byA _(I)(λ)=r _(I) e ^(−2μ) ^(g) ^((λ)z) ^(I)   (15)where z_(I) is the distance of interface I measured from the top surfaceof the sample 205. Next, the differential delay modulator 250 isadjusted again to change the differential delay so that the path lengthtraveled by the mode 001 matches that of radiation reflected frominterface II in the mode 002. The measurement for the interface II isobtained as follows:A _(II)(λ)=r _(II) e ^(−μ) ^(g) ^((λ)z) ^(I) ^(−2μ) ^(h) ^((λ)z) ^(II),  (16)where z_(II) is the distance of interface II measured from interface I.To acquire the absorption characteristics of the layer bounded by theinterfaces I and II, Eq. (7) and Eq. (6) can be used to obtain thefollowing ratio:

$\begin{matrix}{\frac{A_{II}(\lambda)}{A_{I}(\lambda)} = {\frac{r_{II}}{r_{I}}{{\mathbb{e}}^{{- 2}{\mu_{h}{(\lambda)}}z_{II}}.}}} & (17)\end{matrix}$Notably, this equation provides the information on the absorptioncharacteristics of the layer of interest only and this allowsmeasurement on the layer. This method thus provides a “coherence gating”mechanism to optically acquire the absorbance spectrum of a particularand designated layer beneath a sample surface.

It should be noted that the pass band of the optical filter 1610 or 1710may be designed to be sufficiently narrow to resolve the absorptioncharacteristics of interest and at the meantime broad enough todifferentiate the layer of interest. The following example formonitoring the glucose level by optically probing a patient's skin showsthat this arrangement is reasonable and practical.

Various dependable glucose monitors rely on taking blood samples fromdiabetes patients. Repeated pricking of skin can cause considerablediscomfort to patients. It is therefore desirable to monitor the glucoselevel in a noninvasive manner. It is well known that glucose in bloodpossesses “signature” optical absorption peaks in a near-infrared (NIR)wavelength range. It is also appreciated the main obstacle innoninvasive monitoring of glucose is due to the fact that a probinglight beam interacts, in its path, with various types of tissues andsubstances which possess overlapping absorption bands. Extracting thesignature glucose peaks amongst all other peaks has proven difficult.

The above “coherence gating” may be used to overcome the difficulty inother methods for monitoring glucose. For glucose monitoring, thedesignated layer may be the dermis layer where glucose is concentratedin a network of blood vessels and interstitial fluid.

FIG. 19A illustrates an example of a human skin tissue where thecoherence gating technique described here can be used to measure theglucose concentration in the dermis layer between the epidermis and thesubcutaneous layers. The dermis layer may be optically selected andmeasured with the coherence gating technique. It is known that thesuperficial epidermis layer, owing to its pigment content, is thedominant source of NIR absorption. Because of the absence of blood,however, the epidermis yields no useful information for glucosemonitoring. The coherent gating technique can be applied to acquiresolely the absorbance spectrum of the dermis layer by rejecting theabsorptions of the epidermis and the subcutaneous tissues. An additionaladvantage of this technique is from the fact that dermis exhibits lesstemperature variation compared to the epidermis. It is known thatsurface temperature variation causes shifts of water absorption,hampering glucose monitoring.

FIG. 19B shows some predominant glucose absorption peaks in blood in awavelength range between 1 and 2.5 microns. The width of these peaks areapproximately 150 nm. To resolve the peaks, the bandwidth of the tunablebandpass filter may be chosen to be around 30 nm. The depth resolutionis determined by the following equation:

$\begin{matrix}{{\frac{2{\ln(2)}}{\pi}\frac{\lambda_{o}^{2}}{\Delta\lambda}} = {60\mspace{14mu}\mu\; m}} & (18)\end{matrix}$Therefore, the coherence gating implemented with the devices in FIGS. 16and 17 or other optical sensing devices may be used to determine theabsorption characteristics of the glucose in tissue layers no less than60 μm thick. As illustrated in FIG. 19A, human skin consists of asuperficial epidermis layer that is typically 0.1 mm thick. Underneathepidermis is the dermis, approximately 1 mm thick, where glucoseconcentrates in blood and interstitial fluids. The above analysisindicates that it is possible to use the apparatus shown in FIGS. 16 and17 to isolate the absorption characteristics of the dermis from that ofthe epidermis and other layers.

It is clear from Eq. (18) that the product of spectral resolution andlayer resolution is a constant for a given center wavelength λ₀. Thechoice of the filter bandwidth should be made based on the tradeoffbetween these two resolutions against the specific requirements of themeasurement.

The tunable bandpass filter 1610 or 1710 may be operated to acquire theabsorption characteristics of an isolated volume inside a sample.

FIG. 20 illustrates one exemplary implementation of the detectionsubsystem 260 in FIG. 3 where two diffraction gratings 2010 and 2020 areused to separate different spectral components in the output light beamsfrom the polarizing beam splitter 361. A lens 2012 is positioned tocollect the diffracted components from the grating 2010 and focusdifferent spectral components to different locations on its focal plane.A detector array 2014 with multiple photodetector elements is placed atthe focal plane of the lens 2012 so that different spectral componentsare received by different photodetector elements. A second lens 2022 anda detector array 2024 are used in the optical path of the diffractedcomponents in a similar way. In devices shown in FIGS. 5A, 5B, 8A, and8B where a single optical detector is used for measurements, a singlegrating, a lens, and a detector array may be used.

In operation, each detector element receives light in a small wavelengthinterval. The photocurrents from all elements in an array can be summedto form a signal which is equivalent to the signal received in eachsingle detector without the grating shown in FIG. 3. By selectivelymeasuring the photocurrent from an individual element or a group ofelements in an array, the spectral information of the sample can beobtained.

In the above described examples, the optical probe head sends out lightin two different propagation modes where light in one of the two modescarries the information from the sample. Alternatively, light in asingle propagation mode may be used as the input light to the opticalprobe head and as output light from the optical probe head. Hence,devices based on this design not only use a common optical path todirect light to and from the probe head and sample but also control thelight in a single mode. In comparison with above examples where twodifferent modes are used for light coming out of the probe heads, thissingle-mode design further eliminates or reduces any differences betweendifferent modes that propagate in the same optical path.

FIG. 21 shows one exemplary system for acquiring information of opticalinhomogeneity and other properties in substances with only onepropagation mode inside waveguides. A broadband or low-coherence lightfrom Broadband Light Source 201 is directed to a probe head 2110 bymeans of polarization-maintaining waveguides 271 and 272. A partialreflector inside the probe head 2110 reverses the direction of a smallportion of the input light to create a radiation wave 1 whiletransmitting the remainder of the input light to the sample 205.Backscattered or reflected light from the sample 205 becomes a secondradiation wave 2 and is collected by the probe head 2110. The probe head2110 combines and couples both the radiation waves 1 and 2 back into thewaveguide 272. The radiation waves 1 and 2 travel in the waveguide 272towards Light the light director 210 which directs radiation waves 1 and2 through the waveguide 273 towards the detection module 2101. Notably,the radiation waves 1 and 2 output from the probe head 2110 are in thesame mode as the input light to the probe head 2110. the probe head 2110does not change the mode of light when directing the radiation waves 1and 2 to the waveguide 272.

The detection module 2101 includes a beam Splitter 2120, two opticalpaths 2121 and 2122, an optical variable delay element 2123 in the path2122, a beam combiner 2130, and two optical detectors 2141 and 2142. Thebeam splitter 2120 splits the light in the waveguide 273, which includesthe radiation waves 1 and 2 in the same mode, into two parts thatrespectively propagate in the two optical paths 2121 and 2122. Notably,each of the two parts includes light from both the radiation waves 1 and2. The variable delay element or delay line 2123 in the optical path2122 is controlled by a control signal to adjust the relative opticaldelay between the two optical paths 2121 and 2122 and may be implementedby, e.g., the exemplary delay elements described in this application andother delay designs. The beam combiner 2130 combines the signals of thetwo optical paths to overlap with each other and to output two opticalsignals for optical detectors 2141 and 2142, respectively. The beamcombiner may be a polarization beam splitter which splits the combinedlight into two parts, orthogonal in polarization to one another.

The probe head 2110 may include a partial reflector to produce theradiation wave 1 which does not reach the sample 205. Assuming thesingle propagation mode for the light to the probe head 2110 and thelight out of the probe head 21110 is a polarization mode, the lightreflected from the partial reflector in the probe head 2110, i.e., theradiation wave 1, has the same polarization as the light collected fromthe sample, the radiation wave 2. Therefore, both Radiation 1 and 2travel in the same propagation mode in the waveguides, 272 and 273.Because the radiation waves 1 and 2 are reflected from differentlocations, they experience different optical path lengths when reachingthe beam splitter 2120. The effect of variable delay element 2123 is toadd an adjustable amount of the delay in the light in the path 2122relative to the light in the path 2121.

In operation, the variable delay element 2123 can be adjusted so thatthe partial radiation 1 reaching the polarization beam splitter 2130through the path 2122 can be made to experience a similar optical pathlength as the partial radiation 2 reaching the beam splitter 2130 viathe other path 2121. The superposition of the two beams at the photodetectors 2141 and 2142 causes a measurable intensity variation as theirrelative path length is being varied by the variable delay element 2123.This variation can be utilized to retrieve information on theinhomogeneity and other properties of the sample 205.

FIG. 22 shows an exemplary implementation of the system in FIG. 21 usingpolarization maintaining optical fibers. A polarization controller 202may be placed at the output of the light source 201 to control thepolarization of the input light in one polarization mode. The opticalhead 2110 is shown to include a lens system 2111 and a partial reflector2112. Two mirrors 1 and 2 are used to construct the two optical pathsbetween the beam splitters 2120 and 2130. The optical radiationreflected from the partial reflector 2122 and from the sample 205 travelin the polarization-maintaining (PM) fiber 272 in the same mode. Themain portions of the radiation waves 1 and 2 are deflected to the mirror1 while the remaining portions are directed to the mirror 2 by the beamsplitter 2120.

The incident plane of the polarizing beam splitter 2130 can be made tohave a finite angle with respect to the polarization directions of lightfrom both the Mirror 2 in one optical path and the variable delayelement 2123 from the other optical path. In this configuration, lightenergies received by both detectors 2141 and 2142 are the superpositionof the two radiations, i.e., Radiation 1 and Radiation 2. It should beappreciated that the linkage between the beam splitters 2120 and 2130can be made by means of optical fibers or other optical waveguides toeliminate the free space paths and the two mirrors 1 and 2.

In the examples shown in FIGS. 21 and 22, the spacing between theoptical head 2110 and the sample 205 may be greater than the sampledepth of interest so that, upon reaching the beam splitter 2130, thepartial radiation 1 experiences optical path length similar only to thatof partial radiation 2. In other words, split parts of the sameradiation do not experience similar optical path length during theoperation of the systems in FIGS. 21 and 22.

FIG. 23 shows one exemplary optical arrangement for the probe head 2110.The partial reflector 2310 can be realized with a partially reflectivefiber termination, i.e., the end facet of the fiber 272. An uncoatedfiber tip has a reflectivity of approximately 4% and thus may be used asthis partial reflector. Optical coating on the end facet may be used tochange the reflectivity to a desirable value.

The reflectance of the fiber termination 2310 may be chosen based onseveral factors. In one respect, the radiation wave 1 should be strongenough so that its superposition with the radiation wave 2 creates anadequate intensity variation at the two detectors 2141 and 2142. On theother hand, the radiation wave 1 may not be too strong as it mayoverwhelm the photodetectors 2141 and 2142, prohibiting the use of highgain in the detection systems. For optimized operation of the system,one may want to choose the reflectance of the fiber termination to becomparable to the total light collected by the fiber from the sample.

In FIGS. 21 and 22, a common waveguide 272 is used for both sendinginput light into the probe head 2110 and directing output light outputthe probe head 2110. Alternatively, similar to the design in FIG. 15,the waveguide 272 may be replaced by an input waveguide for sendinginput light into the probe head 2110 and an output waveguide directingoutput light output the probe head 2110 to the beam splitter 2120 of thedetection module 2101. In this design, the light director 210 can beeliminated and the optical probe head 2110 may be designed to directoutput light with both the radiation waves 1 and 2 into the outputwaveguide.

Similar to tuning the frequency of light in other examples as described,in implementing the devices in FIGS. 21 and 22, a tunable opticalbandpass filter may be used to tune the frequency band of the light toselectively measure the property of the sample 205 at the frequency bandof the filter. In addition, the use of gratings in the detection moduleto measure different spectral components of the sample as shown in FIG.20 may be used in the module 2101 as well.

FIG. 24 further illustrates the measuring technique for opticallytargeting a layer underneath the surface of a body for its spectralabsorbance. Referring to Equations (15)-(17), the optical differentialdelay can be adjusted to obtain the measurements A_(I) and A_(II) fromthe two depths I and II in order to obtain measurement for the layerbetween the depths I and II. If the center wavelength of the lightsource λ is scanned to obtain measurements at different wavelengths, themeasured ratio in Equation (17) can be used to obtain spectralabsorption characteristics of the substance bounded by interfaces I andII only, i.e. μ_(h)(λ). Therefore, this techniques effectively isolatesthe substance between I and II in terms of its spectral absorbance forthe measurement. This procedure can be carried out for all layers, byvarying the depths of the interfaces I and II, to obtain across-sectional spectral absorbance mapping (SAM).

One way to obtain SAM measurements is to first obtain thecross-sectional maps of the reflectance, A(λ), at two or more differentwavelengths using light radiations centered at these wavelengths. When asingle light source is used as described above, a tunable optical filteris used to select the different wavelengths at each spatial location ofthe probe head over the target area to obtain measurements. Uponcompleting measurements at different wavelengths at one location, theprobe head is moved to the next location and the measurements repeat.This process continues until all locations within the target area aremeasured. This use of the optical differential delay at variable delayvalues and the scan along the target surface in combination effectuatesa 3-dimensional mapping of the spectral absorbance of the target area.

In some applications where the sample has absorption features in a broadspectral range, a single light source may not be able to provide asufficiently broad spectral coverage over these absorption features. Thefollowing sections describe techniques that use two or more lightsources with radiations centered at different wavelengths to provide abroad spectral coverage in SAM measurements.

Various optical arrangements described here can be adopted forperforming SAM measurements. Several examples are described below forusing multiple light sources at different wavelengths.

FIG. 25 shows an optical device 2500 that uses two or more differentlight sources 2510 at different optical wavelengths to obtainreflectance maps from a sample. Each light source emits within abandwidth Δλ centered at a different wavelength from other lightsources. The wavelengths of the light sources 2510 can be selected tocover the spectral range of the absorption features in samples to bemeasured. In some applications, the wavelengths of 2510 may be selectedto effectively sample a specific absorbance feature of interest, asshown in FIG. 31. and thus may not cover other absorption features inthe sample. In a specific implementation, the bandwidth Δλ of each lightsource should be selected with consideration of the depth spatialresolution desired for the measurements. An optical multiplexer 2520 isused to receive the optical radiations from different light sources2510, to combine these optical waves into a common optical path, i.e.,the common optical waveguide 271. The light director 210 directs thecombined optical radiation to the probe head 220 via a common waveguide272. The probe head 220, which is positioned above the sample 205, splita portion of light from the multiplexed or combined optical radiation asthe probe light and direct this probe light to the sample 205. Thereflected light from the sample 205 is collected by the probe head 220and is directed to the differential delay modulator 250 via thewaveguide 272, the light director 210 and another waveguide 273.Details, various implementations and operations of the device 2500 aredescribed in previous sections. An optical demultiplexer 2530 is furtherused to separate the light output from the differential delay modulator250 spatially based on different wavelength bands centered at thedifferent wavelengths of the light sources 2510. Accordingly, an arrayof different optical detector modules 2540 are used to respectivelyreceive and detect the separated beams of different wavelength bands. Asan example, light radiation centered at the wavelength λ₁ and within thebandwidth of Δλ₁ from one light source is separated from the rest andsent to the detector module 1 (D1). Each detector module may include oneor multiple optical detectors. The differential delay modulator 250, thedemultiplexer 2530 and the detector modules 2540 form at least part ofan optical correlator which performs the optical detection of the device2500. The multiplexed light radiations are delivered to the tissuethrough the optical waveguide 272 or fiber and the probe head 220.Backscattered and reflected light from the tissue is collected in partby the probe head 220 and redirected to the optical correlator.

In practice, the probe head 220 is operated to scan the multiplexedlight radiation over the sample 205 to obtain measurements at differentwavelengths. For every designated spatial interval the differentialdelay modulator 250 scans over a range to correspond to a range of depthinside the sample. This process repeats until all sampling locations ofan area of the sample are measured. In this implementation,cross-sectional maps for light radiations at two or more wavelengths canbe simultaneously obtained. While the differential delay modulator 250and the probing light radiation are being scanned, the photocurrentsfrom the detector modules 2540, each receiving light radiation within adifferent wavelength band associated with one of the light sources 2510,can be simultaneously recorded as the data from which the multiplereflectance maps, A(λ₁), A(λ₂) and so on, can be extracted. Eachreflectance map is formed by radiation within the band of one lightsource. These reflectance maps can then be used to derive SAM using analgorithm based on the principles outlined by Equations (15) through(17).

FIG. 26 shows one implementation 2600 of the device 2500 in FIG. 25where a digital signal processor (DSP) 2610 is used to process thedetector outputs from the detector module 2540 and to produce thespectral absorption map. The DSP 2610 may be part of the devicecontroller 370 shown in FIG. 3. A display and user interface module 372is used to allow an operator to view the SAM result and to control thedevice.

FIG. 27 shows an example of the device 2600 in FIG. 26 where thedemultiplexer 2530 is implemented with two gratings 2010 and 2020 andtwo lenses 2012 and 2014. The detector modules 2540 are implemented withtwo detector arrays 2014 and 2024, i.e., each of the detector modules2540 includes one detector in the array 2014 and another detector in thearray 2024 for detecting light at the same wavelength and in differentpolarization states. The polarization beam splitter 361 split thewavelength multiplexed light from the differential delay modulator 250into two beams with mutually orthogonal polarization states where eachsplit beam is a mixture of light in two different modes from the probehead 220. The polarization beam splitter 361 converts a part of receivedlight in the first propagation mode and a part of received light in thesecond propagation mode into light in a third propagation mode thatpropagates along a first optical path and to convert remaining portionsof the received light in the first and the second propagation modes intolight in a fourth propagation mode that propagates along a second,different optical path. The third and fourth modes are two orthogonalpolarization modes of the polarization beam splitter 361.

The gratings 2010 and 2020 separate the wavelength multiplexed lightradiation into angle intervals, each corresponding to the light from oneof the light sources 2510. The number of photosensitive elements in onedetector array can be equal to the number of light sources used. Thesensing area of each of the photosensitive elements may be designed tobe sufficiently large so that all the light radiation within the band ofone light source can be received by one element in the array. Forinstance, if three light sources are used in the system, two arrays eachwith three photosensitive elements may be used.

The optical multiplexer 2520 may be implemented in variousconfigurations. FIG. 28 shows one example of the multiplexer 2520 wherepartially reflective mirrors 2810 and 2802 are used to multiplexradiation beams from three different light sources 2510A, 2510B and2510C. The design can be used with N partially reflective mirrors tomultiplex beams from (N+1) light sources. The partially reflectivemirrors can be manufactured by coating one side of a glass with a thinmetal layer. With this arrangement not all the light power will bemultiplexed into the optical fiber, as loss of optical power occurs ateach reflector. An optical collimator 2810 is used to couple themultiplexed light into the optical waveguide or fiber 271.

FIG. 29A shows another example of the multiplexer 2520 which reduces theoptical loss in the design in FIG. 28 and provides an efficient use ofthe available optical power. In this example, optical dichroic filters2901 and 2902 are used to replace the partially reflective mirrors 2801and 2802, respectively. A Dichroic filter may be implemented in variousforms. One implementation is to use two short-pass interference filtersas the dichroic filters 2901 and 2902.

FIG. 29B shows the optical designs of the dichroic filters 2901 and2902. The cut-off wavelength of the filter 2901 is set between theradiation bands of the first and second light sources centered at λ1 andλ2, respectively; that of the filter 2802 set between the radiationbands of the second and the third light sources centered at λ2 and λ3,respectively. With this arrangement, except for the imperfection of thefilters, all radiation from the three light sources are coupled into theoptical fiber 271 without significant optical loss. Interference opticalfilters of this kind can be fabricated using multilayer dielectric thinfilms. Other possible multiplexers include arrayed waveguide type andgrating type.

In the above devices for SAM measurements, light beams at differentwavelength bands are simultaneously directed by the probe head 220 tothe sample 205. Hence, the optical measurements at different wavelengthsare performed simultaneously. Alternatively, the optical multiplexer2520 may be replaced by an optical switch 3010 as shown in FIG. 30 todirect a probe beam within one of the wavelength bands at a time so thatprobe light beams at different wavelength bands are directed to thesample 205 sequentially at different times to obtain the reflectancemaps. In one implementation, the N broad band light sources 2510 can besequentially linked to the optical device in FIG. 30 through a 1×Noptical switch as the switch 3010. The reflective maps, A(λ₁), A(λ₂) andso on at different wavelength bands are obtained sequentially and arethen used in the calculation of SAM.

The choice of the broadband light sources in any of the above devicedesigns can be made according to the specific absorption features to bemeasured. As an example, FIG. 31 shows an absorbance amplitude spectrum3100 of a sample where an absorption peak 3110 is present. Three or moredifferent broadband light sources with the center wavelengths shown maybe used to map the peak 3110. To achieve a better spectral resolution,the number of the light sources may be increased. In the example ofthree light sources, the reflectance maps at the three differentwavelengths, i.e., A(λ₁), A(λ₂) and A(λ₃), can be used to calculate thestrength of the feature for SAM.

The axial resolution (i.e., the depth resolution) of SAM is related tothe bandwidth (spectral width), Δλ, of the light source at a centerwavelength λ₀ is given by the following:

$\begin{matrix}{{\Delta\; z} = {\frac{2\;{\ln(2)}}{\pi}\frac{\lambda_{o}^{2}}{\Delta\;\lambda}}} & (23)\end{matrix}$For a given bandwidth, Δλ, the depth resolution of the correspondingreflectance map is determined by the above equation. Hence, a broadbandwidth is desirable for resolving a small spatial feature along thedirection of the probe beam, which limits the spectral resolution as atradeoff. For example, if one wants to map an spectral absorbancefeature that occupies a 20 nm range near an optical wavelength of 1 μm,light sources of bandwidth around 5 nm can be chosen. Under theseconditions, the spatial resolution for SAM is roughly 90 μm.

In the above multi-source SAM measurements, each light source has afixed emission center wavelength and a bandwidth. In otherimplementations based on the above-described designs, multiple tunablelaser sources may be used to replace the fixed light sources. Eachtunable laser source may be configured to provide highly coherentradiation over a wavelength range of Δλ centered at λ. Due to the sameconsideration that a spectral absorbance feature of interest may be toobroad for a single tunable laser source to cover, two or more tunablelaser sources, each tunable over a wavelength range centered at adifferent wavelength, can be implemented in various designs for SAMmeasurements.

FIG. 32 illustrates one example of a device 3200 for SAM measurementswhere two or more tunable lasers 3210 are used as the light sources. Theoptical radiations from the tunable laser sources 3210 are combinedthrough the multiplexer 2520 before being guided to the probe head 220.The light waves from the probe head 220, including what is collectedfrom the tissue under examination, are redirected towards thedemultiplexer 2530 where they are separated into separated beams indifferent optical paths according to the wavelength bands, each of whichis received by an optical detector.

This arrangement may be configured to allow for the simultaneous tuningof the wavelengths of the tunable laser sources 3210, which in turnallows for the simultaneous recording of the light waves from the probehead 220 in the different wavelength bands. One feature in the design inFIG. 32 is the lack of the optical differential delay modulator 250 usedin other designs where one or more fixed light sources are used toproduce the probe light. Each tunable laser is tuned through its tuningspectral range during the measurement and the recorded light intensityas a function of the laser wavelength in each of the bands can becomputed to obtain a reflectance map for that band. The reflectancemaps, for the various center wavelengths, can be computed by analyzingthe photocurrents of the photodetectors as functions of the wavelength.A variation of the photocurrent with a certain wavelength periodicityindicates a reflection originated from a certain distance, or depth, inthe sample 205. Such a computation is, in essence, a decomposition ofthe photocurrent according to its frequency, or commonly known as aFourier transformation. In order for the reflectance maps to cover arange of the depth the tunable lasers should have an adequate coherentlength which is comparable or longer than the range of the depth. Two ormore reflectance maps for two or more wavelength bands can be obtainedfor the sample 205 under examination and can be used to derive the SAMof the sample 205 based on Equations (15)-(17).

This use of the tunable lasers may be implemented in the various devicedesigns for SAM measurements by removing the optical differential delaymodulator 250. For example, the design in FIG. 30 may be used, withoutthe differential delay modulator 250, to sequentially direct lightradiations from different tunable laser sources to the sample 205. Whenthe radiation from a particular tunable laser is directed to the sample205, the laser is tuned in its laser frequency through its tuning rangeto obtain measurements of the optical absorption at differentwavelengths within the tuning range.

In some precise optical phase measurements using the above describedtechniques with tunable laser sources, a differential phase modulator250 may be inserted in the common waveguide 273 to receive the lightfrom the probe head in the first and second propagation modes and toproduce and modulate the relative optical phase between the first andsecond propagation modes. The modulation of the relative optical phasebetween the first and second propagation modes causes the photocurrentsout of the photodetectors 2540 (or detectors in the detector arrays 2014and 2024) to shift their peak positions and valley positions withrespect to the wavelength. This allows for accurate calculations of thereflected optical phase of the light reflected from the sample usingmathematical analysis similar to the analysis represented by Equations12 and 13.

As an application of the above non-invasive optical probing techniquesand devices, FIG. 33 shows an example of an integrated system 3300 thatcombines an X-ray CT scan module 3310 for locating pulmonary nodules, aminimally invasive optical probing module 3320, and a treatment module3330 to provide a complete diagnostic and treatment platform fortreating lung cancer. The treatment module 3330 may be designed to useelectromagnetic radiation, such as laser radiation, RF or microwaveradiation energy, to treat a malignant condition at a selected targetarea. A bronchoscope 3340 is used to provide a means for inserting theoptical probe for the optical probing module 3320 into the lung tooptically measure a target area in the lung. In addition, thebronchoscope 3340 is also used to guide the laser beam from the lasertreatment module 3330 to the lung for laser treatment. As illustrated,the bronchoscope 3340 includes a working channel 3342 that is hollow andreceives the optical probe head and optical fiber 3322 for the opticalprobing module 3320 and an optical power delivery waveguide 3322 for thelaser treatment module 3330. The working channel 3342 is inserted insidethe lung to probe different targeted areas in the lung. The distal endof the working channel 3342 includes an end facet or window thattransmits both the optical probe light and the laser beam from the lasertreatment module 3330. A computing and control module 3350 is providedto control the three different modules 3310, 3320 and 3330 and toperform analysis on the measurements. A display and user interfacemodule 3360, which may include a user input interface and a displaymonitor, is used to allow an operator to operate the system 3300.

The CT scan module 3310 is used to scan the lung of a patient to detectand locate all solitary pulmonary nodules (SPNs). Each SPN is visuallylocated via the CT scan imaging. Next, the optical probing module 3320is used to measure each SPN identified by the CT scan. This is adifferential diagnosis and the optical measurement is analyzed todetermine whether each SPN is benign or malignant. The laser treatmentmodule 3330 is then used to treat each malignant SPN. All threeprocedures can be performed in one integrated system.

The minimally invasive optical probing module 3320 may be implemented invarious embodiments as described in this application. As a specificexample, the optical probing module 3320 may be implemented as across-sectional imaging module. The optical module 3320 can be used toallow the anticipated use of CT scans in early stage lung cancerdiagnosis and, in addition, can facilitate cancer therapy using opticalmethods such as Laser Hyperthermia. The module 3320 utilizes opticalcorrelation techniques to obtain optical tomographs to non-destructivelyreveal the tissue structure and other physiological information. Theprobe head of the imaging module 3320 is fiber optic-based and isinserted into the working channel 3342 of the bronchoscope 3340. Thebronchoscope 3340 has been previously used to visually locate the tumorinside the lung. A sequential, in-vivo examination of the suspect tissueor SPN with the optical probing module 3320 can distinguish a calcified,benign SPN from a malignant one by virtue of their different structureand optical properties. This use of the optical probing module 3320resolves the CT scan diagnostic dilemma, enabling an minimally invasiveprocedure to locate SPNs and then identify which nodules are malignant.Notably, the use of this diagnostic sequence based on the opticalprobing allows the physician to avoid most, if not all, pulmonarybiopsies, thereby significantly reducing the risks discussed above andgreatly improving chances for a successful diagnosis without sideeffects.

FIG. 34 illustrates one exemplary use of the system 3300 in FIG. 33. TheCT scan is used to perform the initial examination of the lung to scanfor all SPNs, benign and malignant. After the CT scan, the opticalprobing is performed at each detected SPN to determine whether the SPNis benign or malignant. If a SPN is determined to be malignant, thelaser treatment can be performed to treat the malignant condition of theSPN by using the laser treatment module 3330. If no malignant SPN isfound, the patient may be scheduled for periodic CT scans to monitor thecondition of the lung.

TABLE 1 Assumed Tumor diameter 1 cm. Approx. Tumor Volume 0.5 cc OpticalPower delivered 0.5 watt 1.0 watt 2.0 watts Estimated Laser Power 1.5watt 3.0 watt 6.0 watt Temperature Rise for: 5 sec. Exposure +5 C. +10C. +20 C. 10 sec. Exposure +10 C. +20 C. +40 C.

The laser treatment may be implemented in various configurations such aslaser hyperthermia treatment and laser ablation treatment. For example,a pulmonologist may use a high power laser in the laser treatment module3330 and an optical fiber-based therapeutic probe inserted into theworking channel 3342 of the bronchoscope 3340 to deliver optical powerto the tumor. This procedure, called Laser Hyperthermia, has been shownto necrotize cancerous tissue. The laser emission wavelength is chosenso that essentially all of the light is absorbed by the tissue, e.g.,within first centimeter of tissue. Several types of high power lasersources may be used. For example, compact, powerful diode-pumped solidstate lasers are readily available. Optical fibers capable oftransmitting substantial power levels (e.g., on the order of watts) arealso available. We estimate that coupling of the laser optical power tothe fiber can be accomplished with approximately 33% efficiency usingnormal methods known to practitioners in this field.

As an example, Table 1 lists calculated exposure times needed to elevatethe temperature of the suspect tissue for different optical power levelsdelivered to the tissue. The laser power input to the optical deliverywaveguide 3332 (e.g., optic fiber) would need to be three times higherassuming 33% coupling efficiency. In the above estimates, it is assumethat the malignant tissue behaves thermally as if it were water (about70% accurate) and that the nodule is essentially in poor thermal contactwith the surrounding tissue. Researchers have found that a 10° C. risein temperature is sufficient to kill cancer cells and that highertemperature rises kill malignant cells more quickly. Base upon theresults of Table 1, a 3-6 watt laser should suffice to perform LaserHyperthermia in-vivo with a 5-10 sec. exposure.

The integrated diagnostic and therapeutic system in FIG. 33 and thetechnique in FIG. 34 may be implemented to allow both SPNlocation/detection and bronchoscopic examination to be performed in asingle session or visit. In addition, both differential diagnosis andlaser therapy can therefore be performed during a single bronchoscopicprocedure. Therefore, The three different procedures, SPNdetection/location, malignant-benign differential diagnosis, andremedial therapy, can be performed in a single office visit. A CT Scansystem may be modified to incorporate the much smaller optical devicesfor differential diagnosis and laser therapy so that the completeprocess may be performed on a single piece of equipment. This results invery efficient use of the physician's time and convenience for thepatient. Laser therapy methods, such as laser hyperthermia and laserablation, do not have significant adverse side effects on the patientunder treatment and thus are advantageous in this regard in comparisonwith other therapeutic regimens such as chemotherapy and radiation. Inaddition, the integrated system in FIG. 34 may be implemented to reduceany delay in the differential diagnosis and therapy and thus suchimplementation can be advantageous over other methods that use the‘wait-and-see’ observation of tumor size growth protocol which is oftenemployed to distinguish between malignant and benign SPNs.

The integrated system in FIG. 33 may also be implemented by usingtreatment modules other than laser therapy modules. Variouselectromagnetic radiation therapies using the radiofrequency (RF) energyand microwave energy for ablation may be used. An RF or microwavewaveguide probe may be inserted into the working channel 3342 to deliverthe RF or microwave energy to a targeted SPN for treatment. For example,the laser treatment module 3330 may be replaced by a microwave ablationtherapy unit. The distal end facet of the working channel can be made totransmit both the probe light and the RF/microwave radiation.

In addition, the integrated design shown in FIG. 33 may also beimplemented for diagnosing and treating other illness. In oneimplementation, for example, an integrated diagnostic and treatmentsystem may include a CT scan unit to locate ailing areas in a body part,a referenced cross-sectional imaging unit to analyze each ailing area,and a laser, RF or microwave irradiation therapy unit to treat aselected area. This system may be used to diagnose and treat lungcancer, prostate cancer and other tumors. One specific implementation ofthis system is the example in FIG. 33 for diagnosing and treating lungcancer where a bronchoscope is inserted into the lung for deliver theprobe light and the treatment laser beam.

In implementing the system in FIG. 33, the optical probe head 220 of theoptical imaging module 3320 and the therapy delivery waveguide 3332 maybe unified as a single assembly when inserted inside the working channel3342 so that the treatment radiation, which may be laser radiation, RFor microwave radiation, can be directed to approximately the samelocation where the optical probe head 220 is located. In this design,when a SPN is identified as malignant, the treatment radiation can bedelivered to the same location where the malignant SPN is withoutchanging the location of the distal tip of the working channel 3342.Therefore, this unified assembly may be used to simply the alignment ofthe treatment radiation with respect to a malignant SPN identified bythe optical imaging module 3320.

FIG. 35 shows one example of a unified assembly 3500. A tubular unit orsheath 3510 is used to hold the probe fiber 3322 and the waveguide 3332together as a single unit. The probe head 220 at or near the end of thefiber 3322 and the distal end of the waveguide 3332 are placed next toeach other at the distal end of the tubular unit 3510 within an endfacet window 3520. As such, the probe head 220 and the distal end of thewaveguide 3332 are aimed at the essentially the same location. Theassembly 3500 is then inserted inside the working channel 3342 to placethe end facet window 3520 at the end of the working channel 3342.

Only a few implementations are disclosed in this application. However,it is understood that variations, modifications and enhancements may bemade.

1. A medical device, comprising: a bronchoscope comprising a workingchannel configured for insertion into a passage of a body to reach atarget area inside the body; an optical fiber probe module comprising(1) a probe optic fiber having a portion inserted into the workingchannel of the bronchoscope and (2) an optical probe head coupled to anend of the probe optic fiber and located inside the working channel, theoptical fiber probe module operable to direct probe light to and collectreflected light from the target area in the body through the probe opticfiber and the optical probe head and to obtain information of the targetarea from the collected reflected light; and a laser therapy modulecomprising a power delivery optic fiber having a portion inserted intothe working channel of the bronchoscope to deliver a treatment laserbeam to the target area, wherein the probe optic fiber is structured tosupport light in a first propagation mode and a second, differentpropagation mode, and the optical fiber probe module further comprises:a light source to produce the probe light, wherein the probe optic fiberreceives and guides the probe light in the first propagation mode,wherein the optical probe head is coupled to the probe optic fiber toreceive the light from the probe optic fiber and to reflect a firstportion of the light back to the probe optic fiber in the firstpropagation mode and direct a second portion of the light to thetargeted area, the probe head collecting reflection of the secondportion from the target area and exporting to the probe optic fiber thereflection as a reflected second portion in the second propagation mode;an optical differential delay unit to produce and control a relativedelay between the reflected first portion and the reflected secondportion received from the probe optic fiber in response to a controlsignal; a detection module to receive the reflected first portion andthe reflected second portion from the probe optic fiber and to extractinformation of the target area carried by the reflected second portion;and a control unit, which produces the control signal to the opticaldifferential delay unit, to set the relative delay at two different biasvalues to select a layer of material inside the target area to measurean optical absorption of the selected layer.
 2. The device as in claim1, further comprising: a computed tomography (CT) module to scan atleast a part of the body to obtain CT scan data of the scanned part ofthe body which is analyzed to identify and locate the target areasuspicious of being malignant for further probing and analysis by theoptical fiber probe module.
 3. The device as in claim 1, wherein thedetection module comprises: an optical device to direct light in thefirst propagation mode along a first optical path and light in thesecond propagation mode along a second, different optical path; a firstoptical element in the first optical path to separate light into a firstset of different beams at different wavelengths; a plurality of firstlight detectors to respectively receive and detect the first set ofdifferent beams from the first optical element; a second optical elementin the second optical path to separate light into a second set ofdifferent beams at the different wavelengths; and a plurality of secondlight detectors to respectively receive and detect the second set ofdifferent beams from the second optical element.
 4. The device as inclaim 3, wherein the first and second optical elements are opticalgratings.
 5. The device as in claim 1, wherein the detection modulecomprises a digital signal processor to process information of thetarget area in the reflected second portion and to generate spectralabsorbance data of the target area.
 6. The device as in claim 1, whereinthe optical differential delay unit comprises: a mode splitting unit toseparate received light into a first beam in the first propagation modeand a second beam in the second propagation mode; and a variable opticaldelay element in one of the first and the second beams to adjust anoptical delay between the first and the second beams in response to thecontrol signal.
 7. The device as in claim 1, wherein the first andsecond propagation modes are two orthogonal polarization modes supportedby the probe optic fiber, and wherein the detection module comprises: anoptical detector; and an optical polarizer to receive and mix thereflected first and second portions to produce an optical output to theoptical detector.
 8. The device as in claim 1, wherein the optical probehead comprises a partial mode converter which sets the reflection fromthe target in the second propagation mode.
 9. The device as in claim 1,wherein the optical probe head comprises: a partial reflector to reflectthe reflected first portion of the probe light and to transmit thesecond portion of the probe light to the sample; and a polarizationrotator located between the partial reflector and the target area tochange a polarization of the reflected second portion in controlling thereflected second portion to be in the second propagation mode.
 10. Thedevice as in claim 1, wherein the optical probe head comprises: apartial reflector to reflect the reflected first portion of the probelight and to transmit the second portion of the probe light to thetarget area; and a Faraday rotator located between the partial reflectorand the target area to change a polarization of the reflected secondportion in controlling the reflected second portion to be in the secondpropagation mode.
 11. The device as in claim 1, wherein the opticalprobe head comprises: a partial reflector to reflect the reflected firstportion of the probe light and to transmit the second portion of theprobe light to the target area; and a quarter wave plate located betweenthe partial reflector and the target to change a polarization of thereflected second portion in controlling the reflected second portion tobe in the second propagation mode.
 12. The device as in claim 1, whereinthe optical fiber probe module further comprises: an input waveguide toreceive the probe light from the light source and to guide the inputbeam in the first propagation mode; an output waveguide to receive thereflected first and second portions from the probe optic fiber and todirect the reflected first and second portions to the opticaldifferential delay unit; and an optical router coupled to the inputwaveguide, the probe optic fiber, and the output waveguide, the opticalrouter to direct light coming from the input waveguide to the probeoptic fiber and light coming from the probe optic fiber to the outputwaveguide.
 13. The device as in claim 12, wherein the optical routercomprises: an optical circulator; a first beam splitter in the probeoptic fiber to transmit light in the first propagation mode and toreflect light in the second propagation mode; a second beam splitter inthe output waveguide to transmit light in the first propagation mode andto reflect light in the second propagation mode; and a bypass waveguidecoupled between the first and the second beam splitters to direct thereflected second portion reflected by the first beam splitter to thesecond beam splitter which directs the reflected second portion into theoutput waveguide by reflection.
 14. The device as in claim 12, furthercomprising a tunable optical filter located in one of the inputwaveguide, the probe optic fiber, and the output waveguide to select aportion of the spectral response of the target area to measure.
 15. Thedevice as in claim 1, further comprising a tunable optical filter tofilter the probe light to select a portion of the spectral response ofthe target area to measure.
 16. The device as in claim 1, furthercomprising a tunable optical filter to filter the reflected first andsecond portions to select a portion of the spectral response of thetarget area to measure.
 17. A medical device, comprising: a bronchoscopecomprising a working channel configured for insertion into a passage ofa body to reach a target area inside the body; an optical fiber probemodule comprising (1) a probe optic fiber having a portion inserted intothe working channel of the bronchoscope and (2) an optical probe headcoupled to an end of the probe optic fiber and located inside theworking channel, the optical fiber probe module operable to direct probelight to and collect reflected light from the target area in the bodythrough the probe optic fiber and the optical probe head and to obtaininformation of the target area from the collected reflected light; and alaser therapy module comprising a power delivery optic fiber having aportion inserted into the working channel of the bronchoscope to delivera treatment laser beam to the target area, wherein the optical fiberprobe module further comprises: a plurality of light sources emittinglight at different wavelength bands centered at different wavelengths asthe probe light into the probe optic fiber, wherein the optical probehead reflects a first portion of the probe light back to the probe opticfiber in a first propagation mode and directs a second portion of theprobe light to the target area, and wherein the probe head collectsreflection of the second portion from the target area and exports to theprobe optic fiber the reflection as a reflected second portion in asecond propagation mode different from the first propagation mode; anoptical differential delay unit to produce and control a relative delaybetween the reflected first portion and the reflected second portionreceived from the single waveguide in response to a control signal; adetection module to receive the reflected first portion and thereflected second portion and to extract information of the target areacarried by the reflected second portion; and a probe control unit, whichproduces the control signal to the optical differential delay unit, toset the relative delay at two different bias values to select a layer ofmaterial inside the target area to measure an optical absorption of theselected layer at each and every wavelength from the different lightsources.
 18. The device as in claim 17, further comprising: a computedtomography (CT) module to scan at least a part of the body to obtain CTscan data of the scanned part of the body which is analyzed to identifyand locate the target area suspicious of being malignant for furtherprobing and analysis by the optical fiber probe module.